Encyclopedia of Signaling Molecules

978-1-4419-0460-7......Page 1
HalfTitle Page......Page 2
Title Page......Page 4
Copyright Page......Page 5
Preface......Page 6
About the Editor......Page 8
LOC......Page 10
5-Hydroxytryptamine 2B Receptor......Page 48
Historical Background......Page 49
Physiological Functions in Embryonic Development......Page 51
Physiological Cardiopulmonary Functions......Page 52
Physiological Functions in Central Nervous System......Page 54
In Fibrosis......Page 55
In Bones......Page 56
References......Page 57
Protein Function......Page 59
Regulation of Concentration and Activity......Page 60
Major Sites of Expression and Subcellular Localization......Page 63
Ligands Interacting with the 5-HT2C Receptor......Page 64
References......Page 65
beta-Glucan Receptor......Page 66
mu-Opioid Receptor......Page 67
Historical Background......Page 68
Common Structural Features of ABCA Subfamily Members......Page 69
ABCA Subgroups......Page 70
References......Page 74
Historical Background......Page 75
Role of ACK1 in Signaling Triggered by Cell-Surface Receptors......Page 76
ACK1 in Cancer......Page 78
Summary......Page 79
Activated Cdc42Hs-Associated Kinase 1......Page 80
Historical Background......Page 81
Group II AGS Proteins......Page 83
Group III AGS Proteins......Page 84
References......Page 85
Historical Background......Page 86
ADAP Role in Proliferation and Transcription......Page 87
ADAP Role in Integrin Regulation......Page 88
ADAP Regulation of the Cytoskeleton......Page 91
Summary......Page 94
Historical Background......Page 95
Protein Function and Regulation of Activity......Page 96
Major Sites of Expression and Subcellular Localization......Page 97
Phenotypes and Splice Variants......Page 98
References......Page 99
Historical Background......Page 101
Protein Structure and Regulation......Page 102
Tissue Distribution and Subcellular Targeting......Page 103
Physiological Role and Phenotypes......Page 104
References......Page 105
Topology and Structure......Page 106
Regulation of ACs by G Proteins......Page 107
Additional Modes of AC Regulation......Page 108
In Learning and Memory......Page 109
In Pain......Page 110
In Cardiac Functions......Page 111
In Kidney......Page 112
References......Page 113
Historical Background......Page 114
Posttranslational Processing......Page 116
Ligand Binding......Page 119
Reassembly of Subunits and Receptor (Hetero-)Oligomerisation......Page 122
Coupling to G Proteins......Page 123
Interactions with Other Proteins......Page 124
Summary......Page 126
References......Page 127
AIF Protein Synthesis and Regulation......Page 129
The Involvement of AIF in Cell Death......Page 130
The Involvement of AIF in Cell Survival, Proliferation, and Differentiation......Page 132
The Implication of AIF in Disease......Page 134
aIF6 in Archae......Page 135
Properties of AKAPs......Page 136
Techniques for Identification of AKAPs and Disruption of AKAP-Mediated Protein Kinase a Signaling......Page 138
AKAPs, and Reproduction and Development......Page 139
AKAPs and the Immune System......Page 140
Cancer......Page 141
References......Page 142
Regulation of CD103 Expression......Page 143
CD103+ Dendritic Cells......Page 144
Therapeutic Potential of CD103 Blockade......Page 145
Alpha Polypeptide......Page 146
AR Domains and Function......Page 147
Non-genomic Actions of AR......Page 150
AR and Disease States......Page 151
References......Page 152
Historical Background......Page 153
AT2R Signal Transduction......Page 154
The AT2R Is Important in the Central Nervous System (CNS)......Page 155
The ATR2 Elicits Vasodilatation and Cardioprotection in the Cardiovascular System......Page 156
The AT2R Affects Cancer and Inhibits Inflammation......Page 157
Roles of AT2R in Kidney Disease and Diabetes......Page 158
References......Page 159
A Vital Mitochondrial ADP/ATP Carrier......Page 160
A Lethal Channel......Page 161
ANT1 in Cardiopathy......Page 162
References......Page 163
Historical Background......Page 164
Large Subunits......Page 165
AP-3 Complex Interacting Proteins......Page 166
AP-3 Cargo Proteins......Page 167
ARF1, GEFs, and GAPs......Page 168
Summary......Page 170
Historical Background......Page 171
Function of AP-4: Transport to Lysosomes......Page 172
Function of AP-4: Polarized Sorting......Page 173
Human Diseases: AP-4 Deficiency Syndrome......Page 174
APC......Page 175
Apo2L/TRAIL Signaling......Page 176
Summary......Page 180
A-Protein......Page 181
A-RAF and MAPK Signaling......Page 182
Regulation of Activity......Page 183
A-Raf Interacting Proteins......Page 184
Regulation in Cancer and Other Diseases......Page 186
Summary......Page 187
References......Page 188
Protein Function and Regulation of Activity......Page 189
Phenotypes, Splice Variants, and Disease......Page 191
References......Page 192
Regulation of ARD1 Activity......Page 193
ARD1: Structure/Function......Page 194
ARD1: E3 Ubiquitin Ligase Activity and Arf Domain Function......Page 195
ARD1: Action/Function as TRIM23......Page 196
ARF GAP with Dual Pleckstrin Homology (PH) Domains......Page 197
Function of ArfGAP1......Page 198
References......Page 199
Historical Background......Page 200
Knockout Models Explaining the Physiological Role of ARFRP1......Page 201
Adipocyte-Specific Deletion of Arfrp1 Resulting in Lipodystrophy and Reduced Survival......Page 202
Deletion of Arfrp1 in the Intestine Resulting in Fat Malabsorption......Page 203
Suppression of ARFRP1 Expression in the Brain by Sleep Deprivation......Page 204
References......Page 206
Regulation of Rho-Family GTPase Signaling by ARHGEF25 Proteins......Page 207
ARHGEF25 Protein Regulation of Muscle Physiology......Page 208
Known Protein-Protein Interactions with ARHGEF Proteins......Page 209
References......Page 210
Historical Background......Page 211
Protein Function and Regulation of Activity......Page 212
Major Sites of Expression and Subcellular Localization......Page 213
Phenotypes and Splice Variants......Page 214
References......Page 215
Historical Background......Page 216
ATF3 as a ``Hub´´......Page 217
Other Functions......Page 220
ATF3 in Cancer......Page 221
References......Page 222
AUF1......Page 223
Structure of Aurora Kinases......Page 224
Aurora-A Functions......Page 225
Aurora-B......Page 227
Aurora Kinases and Cancer......Page 228
Summary......Page 229
References......Page 230
BatK......Page 232
Structure and Classification of BCL-2 Proteins......Page 233
Mitochondrial Membrane Permeabilization by BCL-2 Proteins......Page 235
Various Physiological Functions......Page 236
BCL-2 Proteins and Cancer......Page 237
References......Page 238
Historical Background......Page 239
beta-Catenin as a Key Transcriptional Coactivator in the Canonical Wnt Pathway......Page 240
Mechanisms of Target Gene Activation by beta-Catenin......Page 241
beta-Catenin in Development and Disease......Page 242
BIK (BH3 Interacting Killer), NBK......Page 243
Historical Background......Page 244
Pharmacological Aspects......Page 245
Kinins and Disease......Page 246
References......Page 249
Regulation of Gene Expression: mRNA Deadenylation......Page 250
Regulation of Gene Expression: Transcription......Page 251
Effectors of Signaling Pathways......Page 252
Cancer and Tumorigenesis......Page 253
References......Page 255
BY55......Page 256
Historical Background: The Larger Cadherin Superfamily......Page 258
Signaling by Classic Cadherin-Catenin Complexes......Page 262
Signaling by Posttranslational Modification of Classic Cadherins......Page 265
Signaling by Nonclassic Cadherins......Page 268
Summary......Page 270
Calmodulin-Dependent Cyclic Nucleotide Phosphodiesterase......Page 271
Historical Background......Page 272
Physiological Function......Page 273
Summary......Page 274
Historical Background......Page 275
CARMA1 in the Development and Function in T and B Lymphocytes......Page 276
Signaling Regulation of CBM......Page 278
CBM in Lymphomas......Page 279
References......Page 280
Historical Background......Page 281
Structural and Enzymatic Features of CK2......Page 282
Physiological Regulation of CK2......Page 283
Cellular Functions of CK2......Page 285
Emergence of CK2 as a Candidate for Molecular-Targeted Therapy......Page 287
References......Page 288
Caspases......Page 289
Inflammasomes......Page 290
The Extrinsic Pathway......Page 292
The TNFα DISC......Page 295
Regulators of Caspase 8/10......Page 296
Caspase 9 Substrates......Page 297
Apoptotic Caspases: The Executioners......Page 298
Cell Death by Caspases......Page 300
Caspase and Disease......Page 301
References......Page 302
Catnb......Page 303
Cbln1 as a C1q Family Protein......Page 304
A New Comer to the World of Synaptic Organizers......Page 305
Summary......Page 306
CCK-A Receptor......Page 307
CCL3 Gene and Production......Page 308
CCL3 Receptors......Page 309
References......Page 311
Historical Background......Page 312
CCL4 Receptors......Page 313
CCL4 Activities......Page 314
References......Page 315
CCL5 Receptors......Page 316
References......Page 319
Historical Background......Page 320
Molecular action......Page 321
Physiological Function......Page 322
Roles in Pathological Conditions and Wound Healing......Page 323
Gene Regulation......Page 326
References......Page 328
Historical Background......Page 329
The CCT Complex, Its Interacting Proteins and Folding Mechanism......Page 330
CCT: The Cytoskeleton and Cell Cycle Progression......Page 332
Summary......Page 334
Synonyms......Page 335
Structure, Specificity, and Function of CD160......Page 336
CD160 Transmembrane Isoform (CD160-TM): Structure and Function......Page 338
Summary......Page 339
CD247......Page 340
Genomic Organization and Protein Structure......Page 341
Stalk Region......Page 342
Di-Leucine-Based Motif......Page 343
Retention Motif......Page 344
Pathophysiological and Clinical Roles......Page 345
References......Page 346
Historical Background......Page 347
CD38 as an Enzyme......Page 348
CD38 as a Receptor......Page 350
References......Page 352
Introduction......Page 353
Evolution, Genomic Organization, and Protein Structure......Page 354
Assembly and Membrane Organization......Page 355
Phosphorylation and Internalization of CD3zeta......Page 356
Functions......Page 358
References......Page 359
Historical Background......Page 360
CD40 and TRAFs......Page 361
TRAF Recruitment and Degradation......Page 363
Early CD40 Signals......Page 365
Summary......Page 366
Historical Background......Page 367
CD43 Expression is Tightly Controlled......Page 368
A Multifunctional Protein......Page 369
Multiple Ligands for a Multifunctional Protein......Page 370
CD43 is a Pathogen Recognition Receptor......Page 372
CD43: A New ``Kid on the Block´´ in Tumor Development......Page 373
References......Page 374
Synonyms......Page 375
CD45 is a Major Regulator of the Src Family Kinases, Lck and Lyn......Page 376
CD45 and T Cell Antigen Receptor Signaling......Page 377
Regulation of Additional Signaling Pathways by CD45 in Leukocytes......Page 379
References......Page 381
Historical Background......Page 382
NO/cGMP Pathway......Page 383
Cell-Survival Signaling......Page 385
Other Second Messengers......Page 387
Summary......Page 389
Synonyms......Page 390
Tetraspanin Web and CD53 Protein Interactions in Plasma Membranes......Page 391
Tetraspanin Web and CD53 Interactions with Intracellular Signaling......Page 392
References......Page 393
CD72, a Historical Background......Page 395
Functional Role of CD72......Page 396
Signaling Mechanisms Important for the Functional Effects of CD72 in B Cells......Page 397
Functional Effects and Disease Associations of Human CD72......Page 399
References......Page 401
Historical Background......Page 402
Structure......Page 403
Integrins......Page 404
Hepatocytes......Page 405
Synonyms......Page 406
The Role of CD91 in Cell Signaling......Page 407
References......Page 410
CDC2L2......Page 411
Regulation of Expression......Page 412
Substrate Specificity of Cdc7 Kinase......Page 413
Functions During Meiotic Cell Cycle......Page 414
Roles of Cdc7 in Other Chromosome Transactions......Page 415
Cdc7 as a Target for Novel Cancer Therapy......Page 417
References......Page 418
Historical Background......Page 420
CDK11 and Transcription......Page 421
CDK11 and Mitosis......Page 422
CDK11 and Tumorigenesis......Page 423
Summary......Page 424
References......Page 425
Alternative Names......Page 426
Expression Patterns of CEACAMs......Page 427
Functions Mediated by CEACAMs......Page 429
Regulation of the Activity of CEACAMs......Page 430
References......Page 432
Historical Background......Page 433
Interactions with Ligands and Other Proteins......Page 436
CCR1 Antagonists......Page 437
Regulation of Concentration......Page 438
Phenotypes......Page 439
Summary......Page 440
References......Page 441
Tissue Distribution and Physiological Actions of CCK-1 Receptors......Page 442
Structure of CCK-1 Receptors and Molecular Basis of Ligand Binding......Page 443
Signaling at the CCK-1 Receptor......Page 444
Summary......Page 445
Biochemical Characterization......Page 446
Localization......Page 447
Physiological Response to the CCK-2 Receptor Occupation......Page 448
Role of CCK-2R in Cancer......Page 449
Summary......Page 451
c-H-Ras......Page 452
Regulation of CKIP-1......Page 453
Biological Functions of CKIP-1......Page 454
References......Page 455
Historical Background......Page 456
Regulation of CLEC-1 Expression......Page 457
CLEC-1 Function and Regulation of its Activity......Page 458
Clec1a......Page 459
Structure......Page 460
Ligands......Page 461
References......Page 462
Historical Background......Page 463
CLEC4E Expression Pattern and Regulation of Expression......Page 464
CLEC4E Signaling and Regulation of Activity......Page 465
Functional Significance of CLEC4E Signaling......Page 466
References......Page 467
Structure......Page 468
Function......Page 469
Genetics and Splice Variants......Page 470
References......Page 471
Historical Background......Page 472
Function and Ligands......Page 473
Signaling......Page 474
Role in Immunity and Homeostatis......Page 475
References......Page 477
Historical Background......Page 478
Structure of the LAMMER/CLK Kinases......Page 479
LAMMER Kinase Autophosphorylation, Consensus Phosphorylation Sites, and Substrates......Page 480
Mammalian CLKs......Page 482
DOA Kinase of Drosophila......Page 483
Plant LAMMER Kinases......Page 485
LAMMER Kinases on Drugs......Page 486
References......Page 487
Historical Background......Page 489
c-Myb in Stem Cells and Non-hematopoietic Tissues......Page 490
Mechanisms Controlling the Specificity and Activities of c-Myb......Page 491
The Importance of c-Myb as a Human Oncogene......Page 493
References......Page 494
Historical Background......Page 495
Functions of Copines......Page 496
Interaction of Copines with Signaling Proteins......Page 497
A Dual-Function Hypothesis......Page 498
Summary......Page 499
c-Raf-1......Page 500
Gene and Protein Structure......Page 501
CREB Coactivators and CREB-Interacting Proteins......Page 502
Physiological Functions of CREB......Page 503
References......Page 504
Historical Background......Page 505
Function of Csk......Page 506
Regulation of Csk......Page 507
Summary......Page 508
References......Page 509
Historical Background......Page 510
Phenotypes of CTK-Deficient Mice......Page 512
SFK-Dependent and SFK-Independent Functions of CTK......Page 513
The Roles of SH3 and SH2 Domains in Regulation of Kinase Activity and Subcellular Localization of CTK......Page 514
Summary......Page 518
Csnk2......Page 519
Structure......Page 520
Structure of the C-terminal Regulatory Domain......Page 521
Membrane-Associated Receptors and Cytoplasmic Kinases......Page 522
Colon Cancer......Page 523
Pancreatic Cancer......Page 524
Clinical Trials with c-Src Inhibitors......Page 525
References......Page 526
Ctnnb......Page 527
Historical Background......Page 528
CX3CL1 Expression Patterns......Page 529
CX3CL1/CX3CR1 in Microglial Function......Page 530
CX3CL1/CX3CR1 in Cancer......Page 531
References......Page 532
Historical Background......Page 533
CXCL10 in T1DM......Page 535
CXCL10 in T2DM......Page 536
Summary......Page 537
Synonyms......Page 538
Activation of CDKs......Page 539
Transcription......Page 540
Degradation......Page 541
References......Page 542
cyt-PTPe......Page 543
Domain Structure of DAPK and Regulation of Enzymatic Activity......Page 544
Regulation of DAPK Expression......Page 545
Signal Transduction Pathways Involving DAPK and Its Protein Substrates......Page 546
DAPK, Autophagy and Apoptosis......Page 547
Summary......Page 548
Synonyms......Page 549
DARPP-32 Knockout and Mutant Mice......Page 550
Psychiatric Disorders and Neurological Diseases......Page 551
DARPP-32 and Drugs of Abuse......Page 553
References......Page 554
Activation of Cdc7 Kinase by Dbf4 Protein......Page 556
Functions of Dbf4/ASK During Cell Growth......Page 557
Other Dbf4-Related Molecules......Page 558
Summary......Page 559
References......Page 560
Historical Background......Page 561
Extracellular N-Terminal Domain (NTD)......Page 562
Extracellular Ligand-Binding Domain (LBD)......Page 563
References......Page 564
Dfz2......Page 565
Subfamily Classification of Mammalian DHHC Proteins......Page 566
Enzymatic and Regulatory Mechanisms for DHHC Proteins......Page 567
Summary......Page 568
Synonyms......Page 569
Signaling Properties and Regulation......Page 570
Biological Functions......Page 571
References......Page 572
Acknowledgments......Page 802
Molecular Mechanism of DOCK2 as a Rac-Specific GEF (Guanine Nucleotide Exchange Factor)......Page 573
The Immunomodulatory Role of DOCK2 in Lymphocytes......Page 574
Summary......Page 575
Domain Protein......Page 576
Historical Background......Page 577
DRAK2´s Role in Apoptosis......Page 578
Structure/Function of DRAK2......Page 579
Role in Immune System......Page 582
References......Page 583
DTSF......Page 584
DYNLT1/Tctex-1 (AGS2 )......Page 585
Structural Properties......Page 586
Biochemical Functions......Page 587
Regulation of Ect2 by Phosphorylation and Protein Associations......Page 588
Involvement of Tumor Formation......Page 589
References......Page 590
EMT......Page 591
Localization of the ETA Receptor......Page 592
ETAR-Activated Signaling Pathways......Page 593
Ligand Binding, Internalization, and Regulation of Activity......Page 594
ETAR in Disease......Page 595
Summary......Page 597
Endothelin-A Receptor......Page 598
Historical Background......Page 599
General Characteristics......Page 600
Specific Properties......Page 601
Characterization......Page 602
Localization and Function......Page 603
Localization and Function......Page 604
Localization and Function......Page 605
References......Page 606
Characteristics of Ephrins and Eph Receptors......Page 607
Axon Guidance and Topographic Mapping......Page 608
Adhesion Versus Repulsion: Modulation of Ephrin/Eph Interaction and Function......Page 609
Regulation of Actin Cytoskeleton......Page 611
Regulation of Protein Expression Via Transcription, Protein Synthesis, and Degradation......Page 612
References......Page 613
EphA3 Expression......Page 614
Ligands and Mechanisms of Interaction with EphA3......Page 615
Activation and Signal Transduction......Page 616
Biological Functions......Page 617
References......Page 618
Historical Background......Page 621
Domain Organization and Interacting Partners......Page 622
Multiple Functions of Eps8 in the Small GTPase Pathways Control Actin Dynamics-Based Processes......Page 625
Physiological Roles of Eps8: From Cells to Multicellular Organisms......Page 628
Eps8 and Cancer......Page 630
Acknowledgments......Page 631
References......Page 632
Structure of ERK Activation......Page 633
Subcellular Localization of ERK......Page 634
Functions and Substrates of ERK......Page 635
ERK in Human Pathologies......Page 636
Specific Roles of ERK1 and ERK2......Page 637
Summary-Perspectives......Page 638
References......Page 639
Expression of Erk3 and Erk4......Page 640
Regulation of Erk3 and Erk4 Activity and Substrates......Page 641
Physiological Functions of Erk3 and Erk4......Page 642
Ese......Page 643
ER Gene and Protein Structure......Page 644
Mechanisms of ER Signaling......Page 645
Genome-Wide Profiling of ER Gene Expression Programs......Page 646
SERMs in Breast Cancer Treatment......Page 647
References......Page 648
Extracellular Regulated Kinase 1 and 2......Page 649
Historical Background......Page 650
FGF Signaling Cascades......Page 651
Pathological Roles of FGF Signaling......Page 652
Summary......Page 653
FGF13......Page 654
FGF7......Page 655
Immunoreceptor Signaling......Page 656
E- and P-Selectin-Induced Signaling......Page 658
References......Page 659
FHIT is a Tumor Suppressor Gene......Page 660
The Fhit Protein Interactome......Page 661
References......Page 662
Synonyms......Page 663
Fibulin Protein Structure and Their Interaction with Other Proteins......Page 664
Fibulins and Cancer......Page 667
Summary......Page 669
FLJ46592......Page 670
Protein Structure and Domain Organization......Page 671
Interactions......Page 672
Regulation of Expression and Activity......Page 675
References......Page 676
Historical Background......Page 677
Protein Structure and Domain Organization......Page 678
Cellular and Subcellular Localization......Page 680
Variants and Mutants......Page 681
References......Page 682
Historical Background: Discovery and Structure......Page 683
Fn14 Signaling......Page 684
Inflammation......Page 685
Cell Death......Page 686
Systemic Lupus Erythematosus......Page 687
Summary......Page 688
References......Page 689
Structures and Function of FSH-R......Page 690
Temporal and Special Expression of FSH-R......Page 691
Regulation of FSH-R Expression......Page 693
Abnormality of FSH-R......Page 695
Summary......Page 696
Synonyms......Page 697
FPR1-Mediated Phagocyte Functions......Page 698
Diversity of Formyl Peptide Receptor Family Ligand Binding and Downstream Effects......Page 702
References......Page 703
FoxO1 and Glucose Metabolism......Page 704
FoxO1 and Lipid Metabolism......Page 705
Insulin Regulation of FoxO1 Activity......Page 706
FoxO1 Acetylation and Deacetylation......Page 707
Summary......Page 708
FPR......Page 709
FPR2/ALX Expression, Structure, and Agonists......Page 710
FPR2/ALX Signal Transduction......Page 713
FPR2/ALX: Anti-inflammatory, Proresolution, and Therapeutic Potential......Page 714
References......Page 715
ZPK......Page 2076
Historical Background......Page 717
Molecular Structure, Tissue Distribution, and Splicing Variants......Page 718
Possible Mode of Action in Morphological Changes......Page 719
References......Page 720
Frizzled-9......Page 721
Domain Structure of FRS2 Proteins......Page 722
Molecular Functions of FRS2α......Page 723
Molecular Functions of FRS2beta......Page 725
Relevance of FRS2 Proteins to Cancer......Page 726
References......Page 727
Historical Background......Page 728
Canonical WNT Signaling Cascade......Page 729
Noncanonical WNT Signaling Cascades......Page 730
Pathophysiology of Frizzled Family Members......Page 731
References......Page 732
FZD5......Page 733
FZD9......Page 734
Historical Background......Page 736
Role of Gα12 in Cell Growth, Apoptosis, and Oncogenic Transformation......Page 737
Role of Gα12 in Cell Polarity, Adhesion, Migration, and Invasion......Page 738
Receptors and Effectors Coupled to Gα12......Page 740
Role of Gα12 at the Organismal Level: Development and Morphogenesis......Page 742
Summary......Page 743
References......Page 744
Role of Transducin in Phototransduction......Page 745
Transducin Activation......Page 746
Light-Dependent Redistribution of Transducin......Page 747
GNAT1-Independent Phototransduction in Rods......Page 748
Synonyms......Page 749
Historical Background......Page 750
G Protein betagamma Regulation of Effectors......Page 752
G Protein betagamma as a Target for Therapeutic Development......Page 754
References......Page 755
Historical Background: Discovery of G Protein α i as the Inhibitor of Hormone-Stimulated Adenylyl Cyclase Activity......Page 757
Gαi Structure and G Protein Catalytic Mechanism......Page 758
GPCR-Regulated Gi Signaling......Page 760
Gi-Family Regulation of Vesicle-Mediated Protein Transport......Page 762
Gαi Regulation by Accessory Proteins - GPR Motif Proteins and non-receptor GEFs......Page 763
References......Page 765
Historical Background......Page 769
Membrane Targeting......Page 770
Tyrosine Phosphorylation......Page 771
p85 and PI3K Signaling (pY 447, 472, 589)......Page 772
Cross Talk Between PI3K and Shp2......Page 773
Summary......Page 774
Historical Background......Page 775
Gab2 Recruitment to the Receptor......Page 776
Signaling Pathways Activated by Gab2......Page 778
Biological Functions......Page 779
Gab2 in Cancer and Alzheimer´s Disease......Page 780
References......Page 781
Structure of GABAA Receptors......Page 783
Regulation of GABAA Receptor Expression......Page 784
GABAAergic Signaling Is Developmentally Shifted from Depolarizing (Excitatory) to Hyperpolarizing (Inhibitory)......Page 785
References......Page 787
Regulation of Gadd45......Page 788
The Effects and Consequences of Gadd45a Expression......Page 790
Gadd45b and Gadd45g......Page 793
Involvement of Gadd45 in Cancer......Page 794
References......Page 795
GALNR......Page 796
Agonists......Page 797
Galanin Receptor Signaling......Page 798
Pain......Page 800
Tumors......Page 801
Properties and Subtypes of GABA Transporters......Page 803
Stoichiometry and Kinetics of GABA Transporters......Page 805
Summary......Page 806
Historical Background......Page 807
Role of GATA-3 in the Development and Function of Other Hematopoietic Cells......Page 809
GATA-3 in the Context of Other T Cell Transcription Factors......Page 811
GATA-3 and Disease......Page 814
References......Page 815
Historical Background......Page 816
Main Features of Protein Structure......Page 817
Regulation of Guanylate Cyclase Activity......Page 818
References......Page 819
Historical Background......Page 820
Physiological Actions of GIP......Page 821
Structural Organization and Dynamics of GIP-GIPR Interaction......Page 822
Insulin Secretory Pathway......Page 823
beta-Cell Growth and Survival Pathways......Page 824
References......Page 825
Historical Background......Page 826
Ionotropic Glutamate Receptors......Page 827
Metabotropic Glutamate Receptors......Page 831
References......Page 832
Biomembranes and Signal Transduction......Page 833
Receptors......Page 834
The p38 Signal Transduction Pathway......Page 835
Glutathione-S-Transferase......Page 836
Alpha Class......Page 837
Mu Class......Page 838
GSTs as Signaling Molecule......Page 839
References......Page 845
Signaling Pathways Involving GSK-3......Page 846
Genetic Analysis of GSK-3 Functions......Page 848
GSK-3 and Cancer Etiology......Page 850
References......Page 851
GNRP......Page 852
Structure and Activation of GPR84......Page 853
Role in Immune Response......Page 854
Role in Development......Page 855
References......Page 856
Medical Relevance......Page 857
A More Detailed Description of the G-Protein Cycle......Page 858
References......Page 859
Introduction......Page 860
Role of GRK1 in Phototransduction, Oguchi Disease, and Light-Dependent Degeneration......Page 862
Structure/Function of GRK1......Page 863
Regulations of GRK1 Activity......Page 865
Summary......Page 866
References......Page 867
Historical Background......Page 868
Protein Chaperone......Page 870
Immune Regulator......Page 871
Calcium Binding Protein......Page 872
Physiological Function in Embryonic Development......Page 873
Cancer......Page 874
Ischemia-Reperfusion......Page 875
References......Page 876
Gsp1......Page 877
Guanine Nucleotide Exchange Factor, Calcium- and DAG-Regulated......Page 878
Guanylate Cyclase Forms......Page 879
Tissue Distribution......Page 880
Signaling Pathways and Physiological Responses Involving Guanylate Cyclases......Page 881
References......Page 884
Domain Organization of GC-C......Page 885
Regulation......Page 886
Downstream Signaling and Disease Phenotypes......Page 887
References......Page 889
Membrane-Associated Guanylyl Cyclases......Page 890
Guanylyl Cyclase A/Natriuretic Peptide Receptor A (GC-A/NPR-A)......Page 891
Guanylyl Cyclase C (GC-C)......Page 892
Summary......Page 893
Gαt......Page 894
Historical Background......Page 896
Ectodomain Shedding......Page 897
Modes of Action......Page 899
Implications in Pathology......Page 901
References......Page 904
Hematopoietic Progenitor Kinase 1......Page 905
The HIPK2 Protein......Page 906
HIPK2 and the DNA Damage Response......Page 907
HIPK2 in Development......Page 908
HIPK2 and Cancer......Page 910
References......Page 911
Synonyms......Page 912
Distribution......Page 913
Protection Against Neuronal Damage......Page 914
Regulation of Cyclic Nucleotide Signaling......Page 915
Involvement in Other MAP Kinase Cascade Signaling Pathway......Page 916
Summary......Page 917
hnRNP D......Page 918
Historical Background......Page 919
AUF1 Can Compete with PABP in Binding to Polyadenylated Sequences......Page 920
AUF1 Binds to AREs as Part of a Multi-subunit Complex......Page 921
References......Page 922
Expression and Localization of Homer Isoforms......Page 923
Binding Partners of Homer Proteins......Page 924
Summary......Page 925
Synonyms......Page 926
HPK1 Activation and Molecular Interactions......Page 927
Functions in Cellular Activation and Apoptosis Induction......Page 929
HPK1 as a Negative Regulator of Inside-Out Integrin Regulation......Page 930
References......Page 931
Hsp25-Kinase......Page 932
Hyl......Page 933
CaaX/CXC Processing......Page 934
Structure, Interactions, and Regulation......Page 935
Expression and Phenotype......Page 936
Summary......Page 937
IFN-Gamma......Page 938
Induction of IkappaBzeta and Its Functions......Page 939
Physiological Roles of IkappaBzeta......Page 941
Structure-Based Activation and Inhibition Mechanism of Nuclear IkappaBzeta......Page 943
Acknowledgments......Page 945
Introduction......Page 946
IL-6 Receptors and Signaling......Page 947
Negative Feedback Regulation of IL-6 Signaling......Page 948
Th17 Cell Differentiation......Page 949
Ahr Functions in Th17 Cells......Page 950
IL-6 and Th17 Cells in Mouse Autoimmune Disease Models (CIA, EAE)......Page 951
IL-6-Blocking Therapy in Human Autoimmune Diseases......Page 952
Historical Background......Page 953
IL-7 Signaling......Page 954
Developmental Functions of IL-7......Page 955
Control of Homeostasis and Function of Mature Naïve T Cells by IL-7......Page 957
Memory Formation and Persistence......Page 959
IL-7 and Disease......Page 960
Synonyms......Page 961
Biochemical Properties......Page 962
Functions in Innate Immunity......Page 963
References......Page 964
Historical Background......Page 965
IAP Structural Domains......Page 966
IAPs in Apoptosis......Page 967
IAPs in Immune Signaling......Page 968
IAPs in Human Diseases......Page 971
References......Page 972
Id4 Regulates Neural Progenitor Proliferation and Differentiation......Page 973
Id4 Maintains the Stem Cells Compartment in Glioblastoma Multiforme......Page 974
Id4 Controls Mammary Gland Development and Cancer......Page 975
References......Page 976
Interactions with Ligands and Other Proteins......Page 977
References......Page 978
Historical Background......Page 979
IGF1R Signaling Complex......Page 980
Ubiquitously Expressed Adaptors......Page 982
Cellular Responses to IGF1R Activation and Intracellular Signaling Pathways Involved......Page 983
Stress of the ER......Page 984
NF-kappaB Signaling Pathway......Page 985
IRS as a Target of Inflammation-Activated Pathways......Page 986
Summary......Page 987
Historical Background......Page 988
Regulation......Page 989
In Vitro Functions......Page 990
References......Page 991
Historical Background......Page 992
Regulation of α4 Integrin Function......Page 993
Therapeutic Applications......Page 994
References......Page 995
Alpha V Structure......Page 996
Outside-In Signaling......Page 999
Intracellular Binding Partners......Page 1000
Intracellular Signaling......Page 1001
Integrin Alpha V in Angiogenesis and Wound Healing......Page 1002
Integrin Alpha V in the Bone......Page 1004
Summary......Page 1005
Structure......Page 1006
Ligands......Page 1007
Function In Vivo......Page 1008
Historical Background......Page 1009
Ligands......Page 1010
Signaling Function......Page 1011
References......Page 1012
IFN-gamma and IFN-gamma Receptor Complex......Page 1013
IFN-gamma Signaling......Page 1014
Biological Functions of IFN-gamma......Page 1015
IFN-gamma: Friend or Foe to Autoimmune Diseases......Page 1016
IFN-gamma and Cancer......Page 1017
References......Page 1018
Historical Background......Page 1019
Discovery of IP3 and Its Receptors......Page 1020
Ca2+ Signals Evoked by IP3 Receptors......Page 1021
Regulation of IP3 Receptors by IP3 and Ca2+......Page 1022
Putting IP3 Receptors in the Right Place......Page 1023
Structural Determinants of IP3 Receptor Behavior......Page 1024
References......Page 1025
Regulation of IRF5 Biological Function......Page 1026
Role of IRF5 in the Innate Immune Response......Page 1027
Role of IRF5 in SLE Pathogenesis......Page 1028
Summary......Page 1029
References......Page 1030
Historical Background......Page 1031
ITPK1 Regulates the Metabolism of the Ins(3,4,5,6)P4 Signaling Molecule......Page 1032
Biological Significance of ITPK1......Page 1034
References......Page 1036
Historical Background......Page 1037
Synaptic Structure......Page 1038
Synaptic Vesicle Recycling......Page 1040
Summary......Page 1042
References......Page 1043
JBP (c-Jun-Binding Protein)......Page 1046
Killer Lectin-Like Receptors (KLR)......Page 1048
Kss1 (Saccaromyces cerevisiae)......Page 1049
Lafora Disease......Page 1050
Laforin Expression, Isoforms, and Localization......Page 1051
Regulation of Laforin Activity and Concentration......Page 1052
Interactions and Signaling......Page 1054
References......Page 1056
LAMMER Kinases......Page 1057
The Positive Role of LAT in TCR-Mediated Signaling......Page 1058
LAT in Autoimmunity......Page 1059
References......Page 1060
Historical Background......Page 1061
Domain Structure and Function......Page 1062
Regulation of LCoR......Page 1063
Summary......Page 1064
Leukosialin......Page 1065
The LIMK Isoforms......Page 1066
LIMK Substrates: Function and Regulation......Page 1067
Expression and Cellular Localization of LIMK......Page 1069
Summary......Page 1070
References......Page 1071
Low Density Lipoprotein Receptor-Related Protein 1 (LRP1)......Page 1072
Regulation of LOX Expression......Page 1073
LOX in Tumor Development and Invasion......Page 1074
The LOX Propeptide in RAS, NF-kappaB, and FAK Signaling......Page 1075
Summary......Page 1076
LRG-21......Page 1077
Lysyl Oxidase......Page 1078
Historical Background......Page 1080
MALT1 as Part of the CBM Complex......Page 1081
MALT1 as an Adaptor Protein in AgR-Mediated CBM Signaling......Page 1083
MALT1 as a Protease in the Regulation of AgR-Mediated NF-kappaB Signaling......Page 1085
MALT1 Functions Beyond AgR Signaling......Page 1086
Summary......Page 1087
Acknowledgments......Page 1088
Structure, Activation, and Expression......Page 1089
Substrates......Page 1090
Summary......Page 1091
MAP3K11......Page 1092
Historical Background......Page 1093
Substrates......Page 1094
Summary......Page 1095
References......Page 1096
MBP1......Page 1097
Historical Background......Page 1098
The MEK1/2 Subfamily of MAPKKs......Page 1099
MEK1/2 Activity and Its Regulation......Page 1100
Structure-Function Relationships......Page 1101
Subcellular Localization......Page 1102
MEK in Cancer......Page 1103
References......Page 1104
Protein and Gene Structure......Page 1105
Localization......Page 1106
Interaction and Regulation......Page 1107
Regulation of Cytoskeletal Proteins......Page 1108
Cytokine Expression......Page 1109
Summary......Page 1111
Historical Background......Page 1112
Endothelial Cells (ECs)......Page 1113
Prostate Cancer (PCa) Cells......Page 1114
p62......Page 1115
KLFs (Kruppel-Like Factors)......Page 1116
Pharmacological Inhibitors......Page 1117
References......Page 1118
MEL......Page 1121
Synonyms......Page 1122
Phylogeny, Structure, and Regulation......Page 1123
MARKs and Cell Morphology......Page 1124
Role of MARKs in Disease......Page 1125
References......Page 1126
Mitogen-Activated Protein Kinase Kinase Kinase 8......Page 1128
The Subfamilies of MAP Kinases......Page 1129
Structure and Regulation of MAP Kinases......Page 1130
References......Page 1131
Historical Background......Page 1132
Regulation of MKK6 Activity......Page 1133
MKK6 Role in Inflammation......Page 1134
References......Page 1135
Synonyms......Page 1136
Historical Background......Page 1137
RNAi-Mediated Phenotypes of MK-STYX Knockdown......Page 1139
MLCK108......Page 1140
Regulation of MLK3 Activity......Page 1141
MLK3 Signaling Triggered by Cell-Surface Receptors......Page 1142
MLK3 in Cancer......Page 1144
Summary......Page 1145
MLT......Page 1146
Stress Response to IR, Anisomycin, UV, Osmotic Stress, Shiga Toxin, and Ricin......Page 1147
Regulation of the Actin Cytoskeleton......Page 1148
References......Page 1149
Synonyms......Page 1150
Functions of Mps1......Page 1151
Regulation of Mps1......Page 1155
Small Molecule Mps1 Inhibitors......Page 1157
Crystal Structures of Human Mps1 Catalytic Domain: Insights into Mps1 Structural Biology......Page 1158
References......Page 1159
MOZ......Page 1161
MOZ and MORF Acetyltransferase Complexes......Page 1162
MOZ and MORF in Animal Development......Page 1163
Summary......Page 1164
References......Page 1165
Historical Background......Page 1166
pro-uPA-uPAR......Page 1167
Phosphorylation of Endo180......Page 1169
MRV Integration Site 1......Page 1170
Regulation of Msk1 Activity......Page 1171
Msk1 Substrates......Page 1172
Chromatin-Associated Proteins......Page 1173
Neuronal Plasticity......Page 1174
References......Page 1175
Historical Background......Page 1176
The mTORC1 Signaling Network......Page 1177
The mTORC2 Signaling Network......Page 1180
Open Questions and Summary......Page 1182
MTUS1 Isoform 1 (ATIP3)......Page 1183
Historical Background......Page 1184
Structure......Page 1185
MTUS1 Function and Interaction with the AT2-Receptor......Page 1186
MTUS1 in Cancer......Page 1187
References......Page 1188
MUK......Page 1189
The Transcription Factor MYC......Page 1190
MYC in Cell Biology......Page 1192
Regulation of MYC Activity......Page 1193
MYC in Cancer......Page 1194
References......Page 1195
Historical Background......Page 1196
MyD88 Localization and Structure......Page 1197
Universal Role of MyD88 in Signaling......Page 1198
Antagonists of MyD88 Signaling......Page 1200
Multiple Roles of MyD88......Page 1202
References......Page 1204
Myeloid Differentiation Primary Response Gene 88......Page 1206
MLCK-Domain Structure and Human Genetics......Page 1207
Expression of MLCK Isoforms......Page 1208
MLCK and Signal Transduction......Page 1209
MLCK210 as a Signal Integrator......Page 1210
References......Page 1211
Historical Background......Page 1212
Myosin Structure......Page 1213
Function......Page 1214
References......Page 1215
Historical Background......Page 1216
Biochemical and Biophysical Properties......Page 1217
Physiological Function......Page 1218
References......Page 1219
Molecular Structure......Page 1220
Filopodia Formation......Page 1221
Summary......Page 1223
Historical Background......Page 1224
Structure......Page 1225
Biochemical and Mechanical Properties......Page 1226
Function......Page 1227
References......Page 1228
MYST4......Page 1229
Historical Background......Page 1230
Posttranslational Modification......Page 1231
The Mitogen-Activated Protein Kinase Pathway......Page 1232
Cyclic Adenosine Monophosphate and Cyclic Guanosine Monophosphate......Page 1233
Nebula......Page 1234
Historical Background......Page 1235
Mitotic Neks: Nek2, Nek6, Nek7, and Nek9......Page 1236
Checkpoint Neks: Nek10 and Nek11......Page 1240
Signal Transduction Neks: Nek3......Page 1241
Summary......Page 1242
References......Page 1243
NES (Nuclear Export Sequence)......Page 1245
Regulation of Net1 Activity......Page 1246
Regulation of Actin Cytoskeletal Organization by Net1......Page 1247
Net1 and Cancer......Page 1248
Summary......Page 1249
Synonyms......Page 1250
Signal Transduction of NTSR Receptors......Page 1251
Physiological Relevance of CNS NTSR Signaling......Page 1252
Physiological Relevance of Peripheral NTSR Signaling......Page 1253
References......Page 1254
Family and Structure......Page 1255
Regulation......Page 1256
Functions......Page 1258
Pharmacological Modulation of NFAT Activity......Page 1260
References......Page 1261
NF-Kappa-B Inhibitor Zeta......Page 1262
Historical Background: Discovery and Structure......Page 1263
NF-kappaB Activation......Page 1264
Finalization of NF-kappaB Activation......Page 1265
The Role of NF-kappaB Signaling in Disease......Page 1266
Neurological Diseases......Page 1267
References......Page 1268
Historical Background......Page 1269
Transporters and Channels......Page 1270
Receptor Tyrosine Kinases......Page 1271
Acknowledgments......Page 1273
Historical Background......Page 1275
Function and Signaling......Page 1276
Specificities and Recognition Mechanisms: Inhibitory Receptors......Page 1278
Specificities and Recognition Mechanisms: Activating Receptors......Page 1281
Tumor and Viral Evasion Mechanisms......Page 1282
Summary......Page 1283
Synonyms......Page 1284
NKG2D Signaling......Page 1285
NKG2D Ligands......Page 1286
NKG2D Function......Page 1287
References......Page 1288
Distribution and Molecular/Biochemical Characterization of NKp46......Page 1289
NKp46 Ligands......Page 1290
References......Page 1291
Historical Background......Page 1292
Myristoyl-CoA:Protein N-Myristoyltransferase (NMT) and Its Isoforms......Page 1293
Myristoylation and Its Biological Significance......Page 1294
Regulation of N-Myristoyltransferase......Page 1297
Summary......Page 1299
References......Page 1300
Notch and Notch Signaling......Page 1301
Somitogenesis......Page 1302
Oncogenic Function......Page 1303
Drug Development......Page 1305
Alzheimer´s Disease......Page 1306
Connection to Other Signaling Pathways......Page 1307
NR1B2......Page 1308
Domain Structure of Nrf2......Page 1309
Degradation of Nrf2 Protein......Page 1310
Phosphatidylinositol 3-Kinase......Page 1311
The Genes That Contain ARE(s)......Page 1312
Cancer......Page 1313
References......Page 1314
Expression of RIP140 and Its Regulation......Page 1315
Acetylation......Page 1316
Functional Roles of RIP140......Page 1317
Role in Muscle Cells......Page 1318
Cytoplasmic RIP140: Player in Pathophysiology of Metabolic Diseases......Page 1319
References......Page 1320
Nuclear Factor-Kappa-B......Page 1321
Molecular Properties of P2X Subunits......Page 1322
Genomic Organization and Splicing......Page 1323
Regulation of P2X Receptors via Their C-terminal Domain......Page 1324
Pharmacology, Tissue Expression, and Physiological Roles of P2X Receptors......Page 1325
Homomeric P2X3R......Page 1329
Homomeric P2X5R......Page 1330
Homomeric P2X7R......Page 1331
References......Page 1332
Structure and Signaling Properties of P2Y Receptors......Page 1334
Functions of P2Y Receptors......Page 1335
References......Page 1338
Historical Background......Page 1339
PtdIns(4,5)P2, SH3 Domains, and EspFu......Page 1340
WIP: A Major Binding Partner......Page 1342
Common and Distinct Functions of N-WASP and WASP......Page 1343
References......Page 1344
General Physiology and Classification of ORs......Page 1346
OR-Mediated Signal Transduction......Page 1347
Role of ORs in Axon Pathfinding......Page 1348
Other Olfactory Receptors......Page 1349
References......Page 1350
Historical Background......Page 1351
Opioid Receptor Cellular Physiology and Function......Page 1352
Opioid Receptor Structure......Page 1354
Opioid Receptor Isoforms......Page 1355
Summary......Page 1356
References......Page 1358
Ox-44......Page 1359
Historical Background......Page 1360
Regulation of p130Cas Tyrosine Phosphorylation......Page 1361
p130Cas Signaling Functions Leading to Enhanced Cell Motility......Page 1363
Summary......Page 1364
p26......Page 1365
Structure and Signaling Pathways......Page 1366
Structure-Activity Relationship (SAR)......Page 1368
References......Page 1369
Historical Background: The p38 MAPK Family of Stress Response Signaling......Page 1370
The p38 MAPK Family of Stress Signaling Pathways: Tissue Specificities......Page 1371
Substrate Specificity of p38 MAPK Isoforms......Page 1372
Subcellular Localization and Nucleocytoplasmic Transport of the p38 MAPK Signal......Page 1374
Feedback Control of MAPK-Regulated Transcription......Page 1375
Role of p38 MAPK Signaling in Response to Stress Challenges and Aging......Page 1376
References......Page 1377
p50......Page 1378
Historical Background......Page 1379
Origin of the p53 Family......Page 1380
Structure and Posttranslational Modifications......Page 1381
Signaling to p53......Page 1383
Transcription-Dependent p53 Functions......Page 1387
Transcription-Independent p53 Functions......Page 1389
Summary......Page 1390
Acknowledgments......Page 1391
Pak2 Structural Information......Page 1392
Pak2 and Apoptosis......Page 1393
References......Page 1394
PCAF (p300/CBP-Associated Factor)......Page 1395
Historical Background: Identification of PCAF as an Acetyltransferase......Page 1396
Domain Organization and 3D Structure of PCAF......Page 1397
PCAF Function in Development......Page 1398
References......Page 1399
Historical Background......Page 1400
What Is PDE4?......Page 1401
Targeting of PDE4......Page 1402
PDE4 and Disease......Page 1403
Summary......Page 1404
PEA-15 Structure and Binding Partners......Page 1405
PEA-15 in Glucose Transport......Page 1406
PEA-15 in Apoptosis......Page 1407
PEA-15 in Cancer Development and Progression......Page 1408
PEA-15 in the Immune Response and Spatial Learning......Page 1409
References......Page 1410
PFT......Page 1411
Expression Regulation......Page 1412
Role in Cancer......Page 1413
Summary......Page 1414
References......Page 1415
Historical Background......Page 1416
PIP4K Structure......Page 1417
PIP4Kα......Page 1419
PIP4Kbeta......Page 1420
PIP4Kgamma......Page 1421
References......Page 1422
STAT´s Protein Structure and Isoforms......Page 1424
Unphosphorylated STATs in Gene Regulation......Page 1425
The Role of STATs in Cancer......Page 1426
References......Page 1427
Differential Stimulation of PDE1 by CaM and Ca2+......Page 1428
Interaction of the Ca2+ and cAMP Second Messenger Systems......Page 1429
Role of PDE1A2 and PDE1B1 in the Regulation of cAMP Concentration......Page 1431
References......Page 1434
Enzymatic Property......Page 1435
Implication for Cellular Signaling......Page 1436
Inhibitors......Page 1437
References......Page 1438
PI3K Enzymes and Products......Page 1439
PI3K Effectors......Page 1441
PI3K Genetics......Page 1442
PI3K in Disease......Page 1444
PI3K Pharmacology......Page 1445
References......Page 1447
Cytosolic PLA2s (cPLA2s)......Page 1448
Ca2+-Independent PLA2s (iPLA2s)......Page 1450
Secreted PLA2s (sPLA2s)......Page 1452
References......Page 1455
Historical Background......Page 1456
Characterization of PLD......Page 1458
Role of Tyrosine Kinases and Phosphatases in PLD Signaling......Page 1460
Role of Small GTPases in PLD Signaling......Page 1462
Role of PLD in Leukocyte Cell Adhesion and Migration......Page 1463
References......Page 1465
PI5P4K......Page 1466
Controlling Pim-1......Page 1467
Pim-1 and Cell Cycle......Page 1469
Conclusions......Page 1470
Historical Background......Page 1471
Structural and Enzymatic Features of Pin1......Page 1472
Cellular Functions of Pin1......Page 1473
Pin1 in Pathogenesis......Page 1474
References......Page 1475
PK58......Page 1476
Structure of PKD Enzymes......Page 1477
Regulation of PKD Activity......Page 1478
Cellular Localization and Functions......Page 1479
Summary......Page 1480
PKD4......Page 1481
PKR Regulators......Page 1482
PKR Substrates......Page 1483
Summary......Page 1485
Plasma Membrane Ca2+ Pump......Page 1486
General Structure and Isoforms......Page 1487
Regulation and Functional Properties......Page 1488
Tissue and Subcellular Expression......Page 1489
Functions in Health and Disease......Page 1490
References......Page 1492
Historical Background......Page 1493
Interactions with Ligands and Other Proteins......Page 1494
Summary......Page 1495
Polycystines, TRPPs......Page 1496
PP2C Negatively Regulating the Stress-Activated MAPK......Page 1497
Wip1 (PP2Cdelta) Negatively Regulating the p53 Tumor Suppressor......Page 1498
Abi1/2 PP2Cs in Abscisic Acid Signaling in Plants......Page 1499
PPMT......Page 1500
Gene and Protein Structure......Page 1501
Cellular Functions......Page 1502
Loss of Function-Associated Phenotypes......Page 1503
References......Page 1504
Molecular Structure and Regulation......Page 1505
Roles in Cancer......Page 1506
Summary and Perspective......Page 1507
P-Rex2......Page 1508
Structure, Expression, and Regulation of the Prion Protein......Page 1509
Trafficking, Endocytosis, and Recycling of the Prion Protein......Page 1511
Systemic Functions of the Prion Protein......Page 1516
Cellular Functions of the Prion Protein......Page 1518
Summary and Future Directions......Page 1523
PRO2706......Page 1524
Enzyme Structure......Page 1525
Regulation of Farnesyltransferase Activity......Page 1526
Inhibitors of Farnesyltransferase (FTIs)......Page 1527
References......Page 1528
Protein Phosphatase 1, Regulatory (Inhibitor) Subunit 1B......Page 1529
Cellular Localization......Page 1530
PTK6 and Signaling Pathways......Page 1531
PTK6 Expression Profile......Page 1533
References......Page 1534
Historical Background......Page 1535
PSGR as a Biomarker for Prostate Cancer......Page 1536
Mechanisms of Action......Page 1537
References......Page 1538
Historical Background......Page 1539
PI3K Signaling......Page 1540
The PTEN Protein......Page 1541
PTEN Regulation......Page 1542
Summary/Future Directions......Page 1543
Historical Background......Page 1544
Substrates and Interactors of PINK1......Page 1545
Investigating PINK1 Function Using Model Organisms......Page 1546
Mitochondrial Morphology......Page 1547
Mitochondrial Trafficking......Page 1548
Summary......Page 1549
Synonyms......Page 1550
PTPe - The Gene and its Protein Products......Page 1551
Regulation of PTPe Activity......Page 1552
Myelination in the Nervous System......Page 1553
Insulin Receptor Signaling, Glucose Homeostasis and Body Weight Regulation......Page 1554
References......Page 1555
Synonyms......Page 1556
Enzymatic Substrates and Protein-Protein Interactions......Page 1557
References......Page 1558
Historical Background......Page 1559
Function of SHP-1 Domains, Regulation of SHP-1 Activity and Targets......Page 1560
Cancer......Page 1564
Glucose Metabolism (Diabetes)......Page 1565
References......Page 1566
Pyk1......Page 1567
Querkopf......Page 1568
Introduction and Historical Background......Page 1570
Distribution, Subcellular Localization, and Interactions with R7 RGS Proteins......Page 1571
Regulation of the RGS Protein Localization and Activity......Page 1572
Effects on the Proteolytic Stability of the R7 RGS Complexes......Page 1573
References......Page 1574
Historical Background......Page 1575
Rab18 Expression and Subcellular Localization......Page 1576
Regulator and Effector Proteins......Page 1577
References......Page 1578
Historical Background......Page 1579
Rab23 and Primary Cilia......Page 1580
Summary and Perspectives......Page 1582
Synonyms......Page 1583
Rab7a Activation and Localization......Page 1584
Rab7a Effectors in the Control of Endocytic Trafficking......Page 1585
Rab7a in Endosomal Signaling......Page 1592
Acknowledgments......Page 1593
Rab8 Function......Page 1594
Rab8 Effectors, Signaling Integration, and Disease......Page 1596
Rab8a in Cilial Transport......Page 1600
References......Page 1603
Historical Background and Taxonomy......Page 1604
Activation of Rac GTPases and Downstream Signaling......Page 1605
Rac GTPases in Hematopoiesis......Page 1607
References......Page 1608
Historical Background......Page 1609
Structure of Raf and Activation of Its Kinase Function......Page 1610
Raf-1-Containing Complexes and Their Biological Functions......Page 1612
Raf-1 and Cancer......Page 1615
References......Page 1616
Historical Background......Page 1617
RAMP Interactions with Other Receptors......Page 1618
RAMP Expression......Page 1619
Evolutionary Considerations......Page 1620
Historical Background......Page 1621
Role in Nucleocytoplasmic Transport......Page 1622
Role in Mitotic Spindle Organization......Page 1624
Additional Functions of Ran......Page 1626
References......Page 1627
Historical Background......Page 1628
The Role of RANKL in the Bone and the Immune Systems......Page 1629
The Intracellular Signal Transduction of RANKL......Page 1630
RANK and RANKL in Mammary Gland Development and Tumorigenesis......Page 1633
References......Page 1635
RANTES......Page 1636
Historical Background......Page 1637
RapGEF1/C3G......Page 1638
RapGEF3 and 4/Epac1 and 2......Page 1639
RapGEF5/MR-GEF......Page 1640
Phospholipase Cepsi......Page 1641
Summary......Page 1642
Synonyms......Page 1643
Regulation of Ras Activity......Page 1644
Ras in Disease......Page 1646
References......Page 1647
Historical Background......Page 1648
Function......Page 1649
RASA1 in Disease......Page 1650
References......Page 1651
Historical Background......Page 1652
RasGrfs Protein Structure and Domain Distribution......Page 1653
Activation of RasGrfs in Response to Increase in Intracellular Calcium Concentration......Page 1654
Activation of RasGrfs in Response to G-Protein Coupled Receptors (GPCR)......Page 1655
Control of Proteolytic Degradation......Page 1656
Summary......Page 1657
References......Page 1658
RasGRP1 Functions in Developing T Cells......Page 1659
RasGRP1 Functions in Other Blood Cells......Page 1661
RasGRP1 and Autoimmunity......Page 1662
RasGRP1 and Cancer......Page 1664
References......Page 1665
Structure and Regulation of the Activity of Rad......Page 1666
Role of Rad in Ca2+ Channel Activity......Page 1667
Summary......Page 1668
Receptor Related to FPR (RFP)......Page 1669
Historical Background......Page 1670
Recoverin Structure......Page 1671
Molecular Properties of Recoverin......Page 1672
Targets and Functions of Recoverin......Page 1673
Recoverin in Cancer......Page 1674
References......Page 1675
Historical Background......Page 1676
RCAN1 Expression......Page 1677
Domains and Motifs of RCAN1......Page 1678
RCAN1 and Down Syndrome......Page 1679
References......Page 1680
Historical Background: Relaxin Family Peptides and Their Receptors......Page 1682
Structural Features and Functional Domains of RXFP1 and RXFP2......Page 1683
Physiological Roles of Relaxin/RXFP1 and INSL3/RXFP2......Page 1685
References......Page 1689
Molecular Biology of RXFP3 and RXFP4......Page 1690
Signal Transduction Pathways of RXFP3 and RXFP4......Page 1691
Physiological Roles of Relaxin-3......Page 1693
References......Page 1694
Historical Background......Page 1695
Role of RARs in Embryonic Development......Page 1696
Role of RARs in Regulating Cell Proliferation and Cancer......Page 1697
Development of RAR Ligands for Use as Therapeutics......Page 1698
References......Page 1701
Historical Background......Page 1702
RGS Protein Activities......Page 1703
The Conventional RGS Protein Subfamilies......Page 1704
Other RGS Domain-Containing Proteins......Page 1706
RGS Proteins......Page 1707
Regulation of RGS13 Expression......Page 1708
Summary......Page 1709
Rho-Associated Protein Kinase......Page 1710
Regulation of RhoC Activity......Page 1711
RhoC Effectors......Page 1712
Proliferation and Apoptosis Resistance......Page 1713
Summary......Page 1714
Rhodopsin Kinase......Page 1715
Historical Background......Page 1716
Summary......Page 1721
References......Page 1723
Biochemical Characterization of Rin GTPase......Page 1724
Regulation of Rin Activity......Page 1725
Functions of Rin GTPase......Page 1726
Summary......Page 1727
Historical Background......Page 1728
RIN1......Page 1729
RIN2......Page 1730
References......Page 1731
ROCK II......Page 1732
Structure and Function of ROCK Kinases......Page 1733
ROCK in Development......Page 1734
ROCK and Stem Cell Survival......Page 1735
Summary......Page 1736
ROKα......Page 1737
The Proteasome......Page 1738
Roles in Human Disease......Page 1739
References......Page 1740
Synonyms......Page 1741
Rpt and Related AAA+ Proteins in Proteolysis......Page 1742
Substrate Recognition by Proteasomes......Page 1744
Summary......Page 1745
RRAD......Page 1746
Activation Mechanisms......Page 1747
Physiological Functions......Page 1748
References......Page 1749
Rsk-Like (RSKL)......Page 1750
Historical Background......Page 1751
Structure......Page 1752
Protein and Ligand Interactions......Page 1754
Disease......Page 1755
Ryanodine-Sensitive Ca2+ Release Channels......Page 1756
Role of S100 Proteins in Calcium Signaling......Page 1758
Expression and Tissue Specificity......Page 1762
S100 Proteins and Disease......Page 1763
S12......Page 1764
Protein and Splice Variants......Page 1765
References......Page 1766
SARA in TGF-beta1 Signaling......Page 1767
Endocytosis, SARA, and TGF-beta1 Signaling......Page 1768
Putative Physiological Role of SARA......Page 1770
References......Page 1771
SCYB10......Page 1772
Expression......Page 1773
SH2D2A Function......Page 1774
References......Page 1775
Structure and Binding Partners of SHIP Family Members......Page 1776
SHIP: A Checkpoint in PI3K-Dependent Signaling......Page 1777
Role of SHIP in the Immune System: Maintaining a Balance between Inflammatory and Regulatory Cells......Page 1779
SHIP in Cancer and Other Diseases: Opportunities for New Therapies......Page 1780
Summary......Page 1781
Sinc......Page 1782
Structural Organization......Page 1783
Binding Partners of SKAP-HOM......Page 1784
Function of SKAP-HOM......Page 1785
References......Page 1786
Historical Background......Page 1787
Slp1/JFC1......Page 1788
Slp3......Page 1790
Slp4/Granuphilin......Page 1791
Summary......Page 1792
Historical Background......Page 1793
SLP-76 as a Scaffold for Signaling Complexes......Page 1794
Role of SLP-76 in TCR Signaling......Page 1795
SLP-76 Signaling in Other Receptor Systems......Page 1796
SLP-76-Deficient Mice and Defects in Multiple Lineages......Page 1797
References......Page 1798
smMLCK......Page 1799
The SOCS Family......Page 1800
Structure and Mode of Action......Page 1801
Physiological Functions of SOCS Proteins......Page 1802
Further Functions of SOCS within the Immune System......Page 1804
References......Page 1805
Somatostatin Analogues......Page 1806
Intracellular Pathways Coupled to SSTRs......Page 1807
Biological Effects of Somatostatin Receptors......Page 1808
Homo- and Heterodimerization of SST and Dopamine (DA) Receptors......Page 1809
Effect of SST Analogues on Various Tumors......Page 1810
Summary......Page 1811
Historical Background......Page 1812
Sonic Hedgehog Processing and Release......Page 1813
The Primary Cilium......Page 1814
Cytosolic Shh Signaling in the Absence of Ligand......Page 1815
Co-receptors......Page 1816
References......Page 1817
Historical Background......Page 1818
Structure, Biosynthesis, and Metabolism......Page 1819
Occurrence, Source, and Transport......Page 1821
S1P in Health and Disease......Page 1823
Sphingosine-1-Phosphoric Acid......Page 1825
Srx......Page 1826
Expression of SRY During Development......Page 1827
Targets of SRY in the Cell......Page 1829
SRY and Sex Reversal......Page 1830
Nuclear Entry of SRY......Page 1831
References......Page 1833
STAT6......Page 1834
p160 Steroid Receptor Coactivator Family......Page 1835
SRC-3......Page 1836
SRC-1......Page 1837
References......Page 1838
STK17B......Page 1839
Regulation of STEP......Page 1840
Phosphorylation......Page 1841
Local Translation......Page 1842
Oligomerization......Page 1844
Mitogen-Activated Protein Kinases (MAPKs)......Page 1845
Fyn......Page 1846
Alzheimer´s Disease......Page 1847
References......Page 1849
Historical Background......Page 1851
uPAR Structure......Page 1852
Cell Surface uPAR Interactors......Page 1853
uPAR and fMLP Receptors......Page 1854
uPAR as Signal Transducer......Page 1855
Summary......Page 1856
Styxl1......Page 1857
Historical Background......Page 1858
Peroxiredoxins and the Identification of Sulfiredoxin......Page 1859
Mechanism of Action of Sulfiredoxin......Page 1860
Regulation of Sulfiredoxin Expression......Page 1861
References......Page 1862
Historical Background......Page 1863
Involvement in Transcription......Page 1864
SWI/SNF and Histone Acetylation Coordinate to Control Chromatin Structure and Function......Page 1866
Involvement in Double Strand Break Repair and Genome Stability......Page 1868
Involvement of RSC and SWI/SNF in Cell Cycle Control, Differentiation, and Development......Page 1869
References......Page 1871
Synembryn......Page 1873
Major Sites of Expression and Subcellular Location......Page 1874
Function......Page 1875
References......Page 1876
Historical Background......Page 1878
The Centrosomal/Basal Bodies Localization of TBCCD1......Page 1879
TBCCD1: The Nucleus-Centrosome Connection......Page 1880
References......Page 1882
Synonyms......Page 1883
TEAD1......Page 1884
TEAD3......Page 1885
Summary......Page 1886
Acknowledgments......Page 1887
TEF-5......Page 1888
Introduction......Page 1889
The Receptor Transmembrane Domain......Page 1890
Thrombospondin......Page 1892
Function......Page 1893
Expression and Regulation......Page 1894
Physiology......Page 1896
Summary......Page 1898
TIF2......Page 1899
Isolation and Initial Characterization of eIF5......Page 1900
eIF5 Is Not a GTPase Protein, but Rather Functions as a GTPase Activating Protein (GAP)......Page 1901
Role of eIF5 in AUG Start Codon Selection and the Link Between eIF5-Promoted GTP Hydrolysis and AUG Selection......Page 1902
References......Page 1905
Historical Background......Page 1906
eIF6 (Tif6p) is Phosphorylated In Vitro and In Vivo in Mammalian and Yeast Cells......Page 1908
Mechanism of Release of eIF6 (Tif6p) from the pre-60S Particles......Page 1909
Recycling of eIF6: Opposing Action of Casein Kinase 1 and Calcineurin Phosphatase in Nucleo-Cytoplasmic Shuttling of eIF6......Page 1910
Summary......Page 1911
References......Page 1912
Synonyms......Page 1913
TLR4 Structural Features with MD2......Page 1914
Binding of LPS with MD2 and TLR4......Page 1915
Signaling Components Associated with TLR4......Page 1916
Signaling Pathways of TLR4......Page 1917
References......Page 1920
Background......Page 1922
Structure of TLR5 and Flagellin......Page 1923
Myd88-Dependent Pathway......Page 1924
Pathologies Associated with TLR5 Signaling......Page 1925
References......Page 1927
TMEM85 Structure and Function......Page 1929
References......Page 1930
Synonyms......Page 1931
Historical Background......Page 1932
Ligands and its Delivery to TLR3......Page 1933
TRIF-Mediated TLR3 Signaling......Page 1934
Negative Regulation of TLR3 Signaling......Page 1936
Antitumor Effect......Page 1937
References......Page 1938
Tissue Distribution of TLR9......Page 1939
Cancer......Page 1940
Autoimmune Disorders......Page 1941
References......Page 1942
Historical Background......Page 1943
MyD88......Page 1944
Mal Localization......Page 1946
TRIF......Page 1947
TRIF and TLR3/4 Signaling......Page 1948
TRAM......Page 1949
SARM and TLR3/4 Signaling......Page 1950
References......Page 1951
Tpd52 (Mouse)......Page 1952
Expression in Normal and Neoplastic Tissues......Page 1953
Immunotherapeutic Targeting......Page 1954
Cellular Functions......Page 1955
Signalling Functions and Binding Partners......Page 1956
References......Page 1957
Historical Background......Page 1958
Tpl2 Signal Transduction......Page 1959
The Impact of Tpl2 Kinase in Cancer......Page 1961
References......Page 1962
TRAF Family......Page 1963
TRAF6......Page 1964
Role of TRAF6 for Smad-Independent TGFbeta Signaling......Page 1965
References......Page 1966
Structural Features of DR4 and DR5......Page 1968
Caspase-Dependent Apoptosis Signaling......Page 1970
Kinase Activation Signaling......Page 1972
References......Page 1974
TRAIL-R1 (Tumor Necrosis Factor-Related Apoptosis-Inducing ligand Receptor 1)......Page 1975
Discovery of Tribbles Genes......Page 1976
Putative Structure of Tribbles Proteins......Page 1977
Tribbles Mediated Control of Signal Transduction......Page 1978
Tribbles and Disease......Page 1979
References......Page 1980
TRIF-Related Adapter Molecule......Page 1981
Historical Background......Page 1982
TRPC Channels as Signaling Molecules......Page 1983
TRPM Channels as Signaling Molecules......Page 1985
TRPP Channels as Signaling Molecules......Page 1986
TRPV Channels as Signaling Molecules......Page 1987
References......Page 1988
Type II PIP Kinase......Page 1989
TZK......Page 1990
Historical Background......Page 1992
Acute Regulation of Urea Transport by Vasopressin......Page 1993
Phosphorylation......Page 1994
Plasma Membrane Accumulation......Page 1995
Acute Regulation of Urea Transport by Other Factors......Page 1996
UT-A1......Page 1997
UT-A2 Knockout Mice......Page 1998
References......Page 1999
UT-B......Page 2000
Historical Background......Page 2002
VRK3 Signaling......Page 2003
Overview......Page 2004
VAMP Family Members......Page 2005
Structure and Function......Page 2006
VAMP1-3......Page 2007
VAMP7......Page 2008
References......Page 2009
Historical Background......Page 2010
Structure......Page 2011
Biological Activity......Page 2014
Regulation of Biological Activity......Page 2019
Summary......Page 2022
Vav-2 Oncogene......Page 2023
Mechanism of Action, the Vitamin D Receptor......Page 2024
Regulation of Vitamin D Receptor Activity......Page 2025
Biological Functions of the Vitamin D Receptor......Page 2026
Summary; Future Directions......Page 2029
References......Page 2030
Synonyms......Page 2031
Channel Pharmacology......Page 2032
CaV1.x, L-Type Channels: Expression and Disease Association......Page 2034
CaV3.x, T-Type Channels: Expression and Disease Association......Page 2037
References......Page 2038
VRK1 Protein Structure and Subcellular Localization......Page 2039
VRK1 Phosphorylation Targets and Role in Nuclear Dynamics......Page 2040
VRK1 in Human Diseases......Page 2041
References......Page 2042
VRK2 Protein Structure and Subcellular Localization......Page 2043
VRK2 Phosphorylation Substrates and Protein Interactions......Page 2044
VRK2 Modulates MAPK Signaling......Page 2045
References......Page 2046
VRK-3......Page 2047
WASH Protein Structure......Page 2048
WASH Regulatory Complex......Page 2049
WASH Localization and Function......Page 2051
Summary......Page 2053
Wyatt......Page 2054
Ypt7p (Yeast Ortholog)......Page 2056
Historical Background......Page 2058
Structure and Regulation......Page 2059
ZAP-70 in T-Cell Development......Page 2061
Expression and Immunopathological Phenotype......Page 2062
Zinc Finger Protein 202......Page 2064
Zinc Transporters......Page 2065
ZnT5......Page 2066
ZnT8......Page 2067
ZiP8......Page 2068
References......Page 2069
Genomic Structure and Functional Domains......Page 2070
Regulation of ZNF202 Expression and Modulation of ZNF202 Function......Page 2071
Phospholipid Transfer Protein......Page 2072
ATP Binding Cassette Transporters A1 and G1......Page 2073
Hepatic Nuclear Factor 4......Page 2074
Summary......Page 2075