Handbook of Cell Signaling Second Edition

Volume 2

Editors-in-Chief

Ralph A. Bradshaw Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California Edward A. Dennis Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California

->*-*-"NCi '-Si- AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO

ELSEVIER Academic Press is an imprint of Elscvier Contents

VOLUME 2 64. The Negative Regulation of JAK/STAT signaling 467 Contributors xxi James M. Murphy, Gillian M. Tannahill, Preface to the Second Edition xliii Douglas J. Hilton and Christopher J. Greenhalgh Preface to the First Edition xlv 65. Protein Kinase Inhibitors 481 Part II Alexander Levitzki Transmission: Effectors and Cytosolic Events 385 66. Integrin Signaling: Cell Migration, Tony Hunter Proliferation, and Survival 491 J. Thomas Parsons, Jill K. Slack-Davis, Robert W. Section A - Protein Phosphorylation 391 Tilghman, Marcin Iwanicki and Karen H. Martin Tony Pawson 67. Downstream Signaling Pathways: 56. Eukaryotic Kinomes: Genomics and Modular Interactions 501 Evolution of Protein Kinases 393 Bruce J. Mayer Gerard Manning and Tony Hunter 68. Non-Receptor Tyrosine Kinases in T Cell 57. Modular Protein Interaction Domains in Antigen Receptor Function 507 Cellular Communication 399 Susan E. Levin and Arthur Weiss Tony Pawson and Piers Nash 69. Receptor Tyrosine Kinase Signaling and 58. Structures of Serine/Threonine and Ubiquitination 517 Tyrosine Kinases 413 Daniela Hoeller and Ivan Dikic Stevan R. Hubbard

59. Protein Tyrosine Kinase Receptor 70. TGFp Signal Transduction 521 Signaling Overview 419 Cristoforo Silvestri, Rohit Bose, Liliana Attisano and Carl-Henrik Heldin Jeffrey L. Wrana

60. Signaling by the Platelet-Derived 71. Mitogen-Activated Protein Kinases 533 Growth Factor Receptor Family 427 Eric Ho and Jim Woodgett Lars Ronnstrand 72. Recognition of Phospho-Serine/ 61. The Epidermal Growth Factor Receptor Threonine Phosphorylated Proteins by Family 435 Phospho-Serine/Threonine-Binding Wolfgang J. Kostler and Yosef Yarden Domains 539 62. Mechanisms and Functions of Eph Stephen J. Smerdon and Michael B. Yaffe Receptor Signaling 443 Martin Lackmann 73. AMP-Activated Protein Kinase 551 D. Grahame Hardie 63. Cytokine Receptor Signaling 451 Mojib Javadi Javed, Terri D. Richmond and 74. Principles of Kinase Regulation 559 Dwayne L Barber Bostjan Kobe and Bruce E. Kemp Contents

75. Calcium/Calmodulin-Dependent 86. The Structure and Topology of Protein Protein Kinase II 565 Serine/Threonine Phosphatases 677 Mary B. Kennedy David Barford

76. Glycogen Synthase Kinase 3 569 87. Naturally Occurring Inhibitors of Protein Philip Cohen and Sheelagh Frame Serine/Threonine Phosphatases 683 Carol MacKintosh and Julie Diplexcito 77. The PIKK Family of Protein Kinases 575 88. Protein Phosphatase 1 Binding Graeme C. M. Smith and Stephen P. Jackson Proteins 689 Anna A. DePaoli-Roach 78. Histidine Kinases in Two-Component Signaling Pathways 581 89. Protein Serine/Threonine Phosphatase Alia O. Kaserer and Ann H. West Inhibitors and Human Disease 699 79. The EF2K/MHCK/TRPM7 Family of Shirish Shenolikar and Matthew H. Brush Atypical Protein Kinases 587 90. Calcineurin 705 Shari L. Wiseman, Fan-Yan Wei, and Claude B. Klee and Seun-Ah Yang Angus C. Nairn

80. The Leucine-Rich Repeat Receptor 91. Protein Serine/Threonine-Phosphatase Protein Kinases of Arabidopsis 2C (PP2C) 711 thaliana - a Paradigm for Plant LRR His'ashi Tatebe and Kazuhiro Shiozaki Receptors 601 John C. Walker and Kevin A. Lease 92. Approaches to the Identification of Protein Tyrosine Phosphatase 81. Engineering Protein Kinases with Substrates 717 Specificity for Unnatural Nucleotides Anton M. Bennett and Tony Tiganis and Inhibitors 609 Chao Zhang and Kevan M. Shokat 93. Inhibitors of Protein Tyrosine Phosphatases 727 82. Clinical Applications of Kinase Zhong-Yin Zhang Inhibitors in Solid Tumors 615 William Pao and Nicolas Girard 94. Regulating Receptor PTP Activity 737 Aurnab Ghose and David Van Vactor 83. Ubiquitin-mediated Regulation of Protein Kinases in NFK,B 95. CD45 743 Signaling 633 Michelle L. Hermiston, Vikas Gupta and Ming Xu and Zhijian J. Chen Arthur Weiss

84. Global Analysis of Phosphoregulatory 96. Cell-Cycle Functions and Regulation of Networks 645 Cdc14 Phosphatases 749 Janine Mok and Michael Snyder Harry Charbonneau

Section B - Protein Dephosphorylation 657 97. MAP Kinase Phosphatases 755 Nick Tonks Stephen M. Keyse

85. Phosphatase Families 98. SH2 Domain-Containing Protein- Dephosphorylating Serine and Tyrosine Phosphatases 771 Threonine Residues in Proteins 659 Benjamin G. Neel, Gordon Chan, and Patricia T.W. Cohen Salim Dhanji Contents

99. Insulin Receptor PTP: PTP1B 811 110. Phospholipase C 887 Sofi G. Julien and Michel L. Tremblay Hong-Jun Liao and Graham Carpenter

100. STYX/Dead Phosphatases 817 111. Cyclic ADP-ribose and NAADP 893 Matthew J. Wishart Antony Galione and Grant C. Churchill 112. Voltage-Gated Calcium Channels 897 101. Zebrafish and Phosphatase William A. Catterall Function 827 Jeroen den Hertog and Mark van Eekelen 113. Store-Operated Calcium Channels 911 James W. Putney 102. Eyes Absent Protein Tyrosine 2+ Phosphatases: A New Eukaryotic 114. Arachidonic Acid-Regulated Ca Branch of the Haloacid Dehalogenase Channel 915 Superfamily 835 Trevor J. Shuttleworth Carolyn N. Wrobel and llaria Rebay 115. IP3 Receptors 921 103. PHLPP: PH Domain Leucine-Rich Colin W. Taylor and Zhao Ding Repeat Protein Phosphatase 843 Alexandra C. Newton 116. Ryanodine Receptors 927 David H. MacLennan and S. R. Wayne Chen

104. PTEN 849 117. Intracellular Calcium Signaling 937 Lloyd C. Trotman Dagmar Harzheim, H. Llewelyn Roderick and Martin D. Bootman 105. PTP Oxidation 855 Ming-Fo Hsu, Yi-Wei Lou, Yi-Yun Chen and 118. Calcium Pumps 943 Tzu-Ching Meng Ernesto Carafoli, Laura Fedrizzi, Teuta Domi, Francesca Di Leva and 106. Chronophin and Slingshot Cofilin Marisa Brini Phosphatases in Cytoskeletal Regulation 863 119. Sodium/Calcium Exchange 949 Celine DerMardirossian, Timothy Y. Huang and Mordecai P. Blaustein Gary M. Bokoch 120. Ca2+ Buffers 955 107. Large Scale Structural Analysis of Beat Schwaller Protein Tyrosine Phosphatases 871 AlastairJ. Barr and Stefan Knapp 121. Mitochondria as Organizers of the Cellular Ca2+ Signaling Network 963 108. Protein Phosphatases and Circadian Gydrgy Szabadkai and Michael R. Duchen Clocks 877 122. EF-Hand Proteins and Calcium Yanshan Fang and Amita Sehgal Sensing: The Neuronal Calcium Sensor Proteins 973 Section C - Calcium Signal Transduction 883 tee P. Haynes and Robert D. Burgoyne Martin D. Bootman 123. Calmodulin-Mediated Signaling 979 109. Calcium Signalling; Messengers, Anthony R. Means Transport Pathways, Sensors, and Physiological Outcomes 885 124. The Family of S100 Cell Signaling Martin D. Bootman and Proteins 983 H. Llewelyn Roderick Claus W. Heizmann and Gunter Fritz Contents

125. Annexins and Calcium Signaling 995 137. PX Domains 1103 Stephen E. Moss Christian D. Ellson and Michael B. Yaffe

126. Calpain 999 138. FYVE Domains in Membrane Trafficking Alan Wells and Ludovic Leloup and Cell Signaling 1111 127. Calcium Signaling in Smooth Christopher Stefan, Anjon Audhya and Scott D. Emr Muscle 1009 Susan Wray 139. Protein Kinase C: Relaying Signals 128. Calcium Signaling in Cardiac from Lipid Hydrolysis to Protein Muscle 1027 Phosphorylation 1123 K.M. Dibb, A.W. Traffordand D.A. Eisner Alexandra C. Newton

Section D - Lipid-Derived Second 140. Modulation of Monomeric G Proteins Messengers 1031 by Phosphoinositides 1131 Lewis Cantley Sonja Vermeren, Len Stephens and Phillip T. Hawkins 129. Historical Overview: Protein Kinase C, Phorbol Ester and Lipid 141. Phosphoinositides and Actin Mediators 1033 Cytoskeletal Rearrangement 1141 Yasutomi Nishizuka and Ushio Kikkawa Paul A. Janmey, Robert Bucki and Helen L. Yin 130. Type I Phosphatidylinositol 4-Phosphate 5-Kinases (PHP 142. Phosphatidylinositol Transfer 5-kinases) 1037 Proteins 1151 Shamshad Cockcroft K.A. Hinchliffe and R.F. Irvine

131. Type II PIP4-kinases 1043 143. Inositol Pentakisphosphate: A Signal Lucia Rameh Transduction Hub 1159 Stephen B. Shears 132. Phosphoinositide 3-Kinases 1049 David A. Fruman 144. Phospholipase D 1167 Wenjuan Su and Michael A. Frohman 133. PTEN/MTM Phosphatidylinositol Phosphatases 1061 145. Diacylglycerol Kinases 1177 Knut Martin Torgersen, Soo-A Kim and Matthew K. Topham and Steve M. Prescott Jack E. Dixon 146. Sphingosine-1-Phosphate Receptors: 134. The Src Homology 2 Containing An Update 1183 Inositol 5' Phosphatases 1065 Michael Maceyka and Sarah Spiegel Frann Antignano, Jens Ruschmann, Melisa Hamilton, Victor Ho, Vivian Lam, Etsushi Kuroda, Laura M. Sly and Gerald Krystal 147. Lysophosphatidic Acid and Sphingosine-1 -Phosphate Activation of 135. Structural Principles of Lipid Second G-Protein-Coupled Receptors 1191 Messenger Recognition 1085 Tetsuji Mutoh and Jerold Chun Roger L. Williams 148. The Role of Ceramide in Cell 136. Pleckstrin Homology (PH) Regulation 1201 Domains 1093 Leah J. Siskind, Thomas D. Mullen and Mark A. Lemmon Lina M. Obeid Contents IX

149. Role of Phospholipase A2 Forms in 160. Signaling and the Immunological ArachidonicAcid Mobilization and Synapse 1283 Eicosanoid Generation 1213 Emanuele Giurisato and Andrey S. Shaw Jesus Balsinde and Edward A. Dennis 161. The Ubiquitin-Proteasome 150. Prostaglandin Mediators 1219 System 1293 Emer M. Smyth and Garret A. FitzGerald Mark Hochstrasser

151. Leukotriene Mediators 1229 162. Caspases: Cell Signaling by JesperZ. Haeggstrom and Anders Wetterholm Proteolysis 1297 Guy S. Salvesen 152. Lipoxins and Aspirin-Triggered 15-epi-Lipoxins: Pro-Resolving 163. MAP Kinase in Yeast 1303 Mediators in Anti-Inflammation Rupam Sahoo, Amjad Husain, and Elaine A. Elion and Resolution 1235 Charles N. Serhan 164. Mammalian MAP Kinases 1315 Norman J. Kennedy and Roger J. Davis

Section E - Protein Proximity 165. Subcellular Targeting of PKA through Interactions 1243 AKAPs: Conserved Anchoring and John D. Scott Unique Targeting Domains 1329 • Mathew D. Pink and Mark L. Dell'Acqua 153. Protein Proximity Interactions 1245 Matthew G. Gold and John D. Scott 166. AKAP Transduction Units: Context dependent Assembly of Signaling 154. Rapid Characterization of in vivo Complexes 1337 Phosphorylation Sites and the Protein John D. Scott and Lorene K. Langeberg Kinases and Phosphatases that Regulate them by Affinity Capture 1247 167. Dendritic Protein Phosphatase TimothyA.J. Haystead Complexes 1343 Anthony J. Baucum II and Roger J. Colbran 155. FRET Analysis of Signaling Events in Cells 1253 168. Protein Phosphatase 2A 1353 Peter J. Verveer and Philippe I.H. Bastiaens Adam M. Silverstein, Anthony J. Davis, Vincent A. Bielinski, Edward D. Esplin, 156. The Focal Adhesion: A Network of Nadir A. Mahmood and Marc C. Mumby Molecular Interactions 1259 Jianxin A. Yu, Nicholas O. Deakin and 169. 14-3-3 Proteins 1367 Christopher E. Turner Hubert Hondermarck

157. WASP and WAVE Family Protein 170. Protein Interaction Data Complexes 1265 Resources 1375 Frank M. Mason and Scott H. Soderling Ian M. Donaldson

158. Synaptic NMDA-Receptor Signaling Complex 1271 Section F - Cyclic Nucleotides 1387 Mary B. Kennedy Jackie D. Corbin

159. Toll Family Receptors 12 77 171. Adenylyl Cyclases 13 89 Yann Hyvert and Jean-Luc Imler Adam J. Kuszak and Roger K. Sunahara Contents

172. Guanylyl Cyclases 1399 182. Substrates of Cyclic Nucleotide- Lincoln R. Potter Dependent Protein Kinases 1489 Ne/7 F. W. Saunders, Ross I. Brinkworth, 173. Phosphodiesterase Families 1409 Bruce E. Kemp and Bostjan Kobe James Surapisitchat and Joseph A. Beavo 183. Physiological Substrates of PKA and PKG 1497 Anja Ruppelt, Nikolaus G. Oberprieler, 174. The cAMP-Specific George Magklaras and Kjetil Tasken Phosphodiesterases: A Class of Diverse Enzymes that Define the 184. Effects of cGMP-Dependent Protein Properties and Localization of Kinase Knockouts 1515 cAMP Signals 1415 Franz Hofmann and Thomas Kleppisch James L. Weeks II and Marco Conti 185. Cyclic Nucleotide-Regulated Cation Channels 1519 175. cAMP/cGMP Dual-Specificity Martin Biel Phosphodiesterases 1425 Lena Stenson, Eva Degerman and 186. Epac, cAMP-Regulated Guanine Vincent C. Manganiello Nucleotide Exchange Factors for Rap1 and Rap2 1525 176. Phosphodiesterase-5 1439 Holger Rehmann, Johan de Rooij and Sharron H. Francis and Jackie D. Corbin Johannes L. Bos

X77. Function and Regulation of 187. Cyclic Nucleotide-Binding GAF Photoreceptor Phosphodiesterase Domains in Phosphodiesterases and (PDE6) in the Visual Signaling Adenylyl Cyclases 1 531 Sergio E. Martinez, Clemens C. Heikaus and Pathway 1445 Joseph A. Beavo Rick H. Cote and Karyn B. Cahill 188. Use of Chimeric Adenylyl Cyclases 178. Regulation of Cyclic Nucleotide Levels to Study Cyclic Nucleotide by Sequestration 1453 Signaling 1537 Jackie D. Corbin, Jun Kotera, Jiirgen LJ. Linder and Joachim E. Schultz Venkatesh K. Gopal, Gary Z. Morris, Rick H. Cote and Sharron H. Francis 189. Cyclic Nucleotide Signaling in the Kinetoplastids 1543 179. cAMP-Dependent Protein Kinase 1461 Stefan Kunz, Mihaela Minca, Susan S. Taylor and Elzbieta Radzio-Andzelm Edith Luginbiihl, Patrick Bregy and Thomas Seebeck

180. Cyclic GMP-Dependent Protein 190. Cyclic Nucleotide Specificity and Kinase: Targeting and Control of Cross-Activation of Cyclic Nucleotide Expression 1471 Receptors 1549 Thomas M. Lincoln, Hassan Sellak, John B. Shabb Nupur Dey, Chung-Sik Choi, and Felricia Brown 191. Cyclic Nucleotide Analogs as Tools to Investigate Cyclic Nucleotide 181. Inhibitors of Cyclic AMP- and Cyclic Signaling 1555 GMP-Dependent Protein Kinases 1479 Anne Elisabeth Christensen, Kristin Viste and Wolfgang R. Dostmann and Christian K. Nickl Stein Ove Doskeland Contents XI

192. cGMP and PKG Signaling in 203. Effectors of Cao 1655 Platelets 1563 Yana Zorina, Ravi lyengar, and Stepan Gambaryan and Ulrich Walter Kenneth D. Bromberg

193. Use of siRNA and Antisense 204. Mono-ADP-ribosylation of Knockdown to Study the Regulation Heterotrimeric G Proteins 1665 ofPKAbyPKI 1569 Maria Di Girolamo and Daniela Corda Edward M. Greenfield and Xin Chen 205. Specificity of G Protein (3^ Dimer 194. Cyclic Nucleotide Signaling in the Signaling 1673 Central Nervous System 1573 Carl A. Hansen, William F. Schwindinger and Diego A. Golombek and Patricia V. Agostino Janet D. Robishaw

195. Compartmentation of cAMP in 206. The Superfamily of "Regulator of cardiomyocytes 1581 G-protein Signaling" (RGS) Gregoire Vandecasteele and Rodolphe Proteins 1683 Fischmeister Melinda D. Willard, Francis S. Willard and David P. Siderovski 196. Phosphodiesterase-9A: cGMP-Specific Enzyme 1589 207. G-Protein Signaling in Jun Kotera, Takashi, Sasaki, and Kenji Omori Chemotaxis 1705 Jonathan Franca-Koh, Stacey Sedore Willard and Peter N. Devreotes Section G - G Proteins 1595 Heidi E. Hamm 208. Reversible Palmitoylation in G Protein Signaling 1713 197. Signal Transduction by G Proteins: Basic Philip B. Wedegaertner Principles, Molecular Diversity, and Structural Basis of Their Actions 1597 209. G Proteins in Gustatory Lutz Birnbaumer Transduction 1721 Bedrich Mosinger, Sami Damak and 198. Heterotrimeric G-Protein Signaling at Robert F. Margolskee Atomic Resolution 1615 David G. Lambright 210. Regulation of Synaptic Fusion by Heterotrimeric G Proteins 1727 199. In Vivo Functions of Heterotrimeric Simon Alford, Edaeni Hamid, Trillium Blackmer, and G Proteins 1621 Tatyana Gerachshenko Stefan Offermanns 211. G-protein Regulation of Channels 1735 200. Regulation of G Proteins by Covalent Ofer Wiser and Lily Yeh Jan Modification 1629 Benjamin C. Jennings and Maurine E. Linder 212. Ras and Cancer 1741 Frank McCormick 201. G-Protein-coupled Receptors, Signal Fidelity, and Cell Transformation 1635 213. The Influence of Intracellular Location Todd R. Palmby, Hans Rosenfeldt, and on Function of Ras Proteins 1 745 J. Silvio Gutkind Jodi McKay and Janice E. Buss

202. Signaling through Gz 1 649 214. Role of R-Ras in Cell Growth 1 753 Michelle E. Kimple, Rainbo C. Hultman and Gretchen A. Repasky, Adrienne D. Cox, Ariella B. Patrick J. Casey Hanker, Natalia Mitin and ChanningJ. Der Contents

215. The Ran GTPase: Cellular Roles and Section H - Developmental Signaling 1865 Regulation 1763 Geraldine Weinmaster Mary Dasso 227. Interactions between Wnt/|3-catenin/ 216. Regulation of NADPH Oxidases by Rac Fgf and Chemokine Signaling in GTPase 1773 Lateral Line Morphogenesis 1867 Gary M. Bokoch, Davide Gianni, Jun-Sub Kim and Tatjana Piotrowski Yu-Ya Kao 228. Wnt Signaling in Development 1873 217. The Role of Rac and Rho in Cell Cycle Stefan Rudloff, Daniel Messerschmidt and Progression 1781 RolfKemler Laura J. Taylor and Dafna Bar-Sagi 229. Hedgehog Signaling in Development 218. Cdc42 and its Cellular Functions 1785 and Disease 1879 Qiyu Feng and Richard A. Cerione Frederic de Sauvage

219. Tissue Transglutaminase: A Unique 230. Regulation of Vertebrate GTP-binding/GTPase 1795 Left-Right Axis Development Marc Antonyak and Richard A. Cerione by Calcium 1885 Adam D. Langenbacher and 220. Roles for ADP-Ribosylation Factors in Ja'u-Nian Chen Membrane Traffic 1803 Amanda Caster and Richard A. Kahn 231. LIN-12/Notch Signaling: Induction, Lateral Specification and Interaction with the EGF/Ras 221. Yeast Small G Protein Function: Pathway 1891 Molecular Basis of Cell Polarity in Sophie Jarriault Yeast 1813 Keith C. Kozminski and Hay-Oak Park 232. Proteolytic Activation of Notch Signaling: Roles for 222. Farnesyltransferase Inhibitors 1819 Ligand Endocytosis and James J. Fiordalisi and Adrienne D. Cox Mechanotransduction 1897 James T. Nichols and 223. Structure of Rho Family Targets 1827 Gerry Weinmaster Helen R. Mott and Darerca Owen 233. BMPs in Development 1905 Kelsey N. Retting and Karen M. Lyons 224. Structural Features of RhoGEFs 1843 Jason T. Snyder, Kent L. Rossman, David K. Worthylake, and John Sondek 234. Neurotrophin Signaling in Development 1913 Katrin Deinhardt and 225. Structural Considerations of Small Moses V. Chao GTP-Binding Proteins 1849 Alfred Wittinghofer 235. Mechanisms Underlying Context-Dependent VEGF 226. Mx Proteins: High Molecular Signaling for Distinct Biological Weight GTPases with Antiviral Responses 1919 Activity 1855 M. Luisa Iruela-Arispe and Georg Kochs and Otto Haller SunyoungLee Contents XIII

236. Vascular Endothelial Growth Factors Parti and Receptors: Signaling in Vascular Initiation: Extracellular and Development 1927 Membrane Events 5 Anna Dimberg, Charlotte Rolny, Laurens A. van Meeteren, and James A. Wells Lena Claesson-Welsh Section A - Molecular Recognition 9 237. Signaling from Fibroblast Growth Ian Wilson Factor Receptors in Development and 2. Structural and Energetic Basis of Disease 1939 Molecular Recognition 11 Kristine A. Drafahl, Emil Alexov and Barry Honig Christopher W. McAndrew, and Daniel J. Donoghue 3. Free Energy Landscapes in Protein- 238. The Role of Receptor Protein Protein Interactions 15 Tyrosine Phosphatases in Axonal Jacob Piehler and Gideon Schreiber Pathfinding 1949 4. Molecular Sociology 23 Andrew W. Stoker Irene M. A. Nooren and Janet M. Thornton

239. Attractive and Repulsive Signaling in 5. Antibody-Antigen Recognition and Nerve Growth Cone Navigation 1955 Conformational Changes 29 Guo-li Ming, and Mu-ming Poo Robyn L. Stanfield, and Ian A. Wilson

240. Semaphorins and their Receptors in 6. Binding Energetics in Antigen-Antibody Vertebrates and Invertebrates 1961 Interfaces 37 Eric F. Schmidt, Hideaki Togashi, and Roy A. Mariuzza Stephen M. Strittmatter 7. Immunoglobulin-Fc Receptor 241. Signaling Pathways that Regulate Interactions 41 Cell Fate in the Embryonic Jenny M. Woof Spinal Cord 1967 Matthew T. Pankratz and Samuel L. Pfaff 8. Ig-Superfold and its Variable Uses in Molecular Recognition 49 242. Cadherin Regulation of Adhesive Nathan R. Zaccai and E. Yvonne Jones Interactions 1975 Barbara Ranscht 9. T Cell Receptor/pMHC Complexes 55 Markus G. Rudolph, Robyn L. Stanfield, and 243. Integration of BMP, RTK and Ian A. Wilson Wnt Signaling through Smadi Phosphorylations 1989 10. Mechanistic Features of Cell-Surface Luis C. Fuentealba, Edward Eivers, Adhesion Receptors 63 Hojoon X. Lee and E. M. De Robertis Steven C. Almo, Anne R. Bresnick, and Xuewu Zhang

VOLUME 1 11. The Immunological Synapse 71 Michael L. Dustin Contributors xxi Preface to the Second Edition xliii 12. NK Receptors 77 Preface to the First Edition xlv Roland K. Strong

1. Cell Signaling: Yesterday, Today, and 13. Carbohydrate Recognition and Tomorrow 1 Signaling 85 Ralph A. Bradshaw and Edward A. Dennis James M. Rini and Hakon Leffler Contents

14. Rhinovirus-Receptor Interactions 93 26. Protease-Activated Receptors 171 Elizabeth A. Hewat Shaun R. Coughlin

15. HIV-1-Receptor Interactions 97 27. Agonist-Induced Desensitization and Peter D. Kwong Endocytosis of G-Protein-Coupled Receptors 177 16. Influenza Virus Neuraminidase Michael Tanowitz and Mark von Zastrow Inhibitors 103 Garry Taylor and Rupert Russell 28. Functional Role(s) of Dimeric Complexes Formed from G-Protein 17. Structural Basis of Signaling Events Coupled-Receptors 185 Involving Fibrinogen and Fibrin 111 Raphael Rozenfeld and Lakshmi A Devi Russell F. Doolittle 29. Chemotaxis Receptors in Bacteria: 18. Structural Basis of Integrin Transmembrane Signaling, Sensitivity, Signaling 115 Adaptation and Receptor Clustering 195 Robert C. Liddington Weiru Wang and Sung-Hou Kim

19. Structures of Heterotrimeric G Proteins 30. An Overview of Ion Channel and their Complexes 119 Structure 201 Stephen R. Sprang Daniel L. Minor

20. G Protein-Coupled Receptor 31. Molecular Mechanism of Store- Structures 129 Operated Ca2+ Signaling and CRAC Veli-Pekka Jaakola and Raymond C. Stevens Channel Activation Mediated by STIM & Orai 209 21. Toll-Like Receptors-Structure and Aubin Penna, Shenyuan L. Zhang, Signaling 139 Andy V. Yeromin, and Michael D. Cahalan Istvan Botos and David R. Davies 32. Ion Permeation: Mechanisms of Ion 22. Variable Lymphocyte Receptors 145 Brantley R. Herrin and Max D. Cooper Selectivity and Block 217 Bertil Hille

Section B - Multi-pass Receptors 149 33. Nicotinic Acetylcholine Receptors 221 James A. Wells Arthur Karlin

23. Structure and Function of G-Protein- 34. Ion Channels Regulated by Direct Coupled Receptors: Lessons from Binding of Cyclic Nucleotides 225 Recent Crystal Structures 151 Edgar C. Young Thomas P. Sakmar Section C - Horizontal Receptors 233 24. Chemokines and Chemokine Receptors: Robert M. Stroud Structure and Function 157 Carol J. Raport and Patrick W. Gray 35. Overview of Cytokine Receptors 235 Robert M. Stroud

25. The (32 Adrenergic Receptor as a Model for G-Protein-Coupled Receptor 36. Growth Hormone and Prolactin Structure and Activation by Diffusible Family of Hormones and Receptors: Hormones 163 The Structural Basis for Receptor Daniel M. Rosenbaum, S0ren G. F. Rasmussen and Activation and Regulation 237 Brian K. Kobilka Anthony A. Kossiakoff and Charles V. Clevenger Contents xv

37. Erythropoietin Receptor as a Paradigm Section D - Membrane Proximal Events 337 for Cytokine Signaling 245 James A. Wells Deborah J. Stauber, Minmin Yu, and Ian A. Wilson 49. Tumor Necrosis Factor Receptor- 38. The Fibroblast Growth Factor (FGF) Associated Factors in Immune Receptor Signaling Complex 253 Signal Transduction 339 Wallace L. McKeehan, Fen Wang and Yongde Luo Qian Yin, Su-Chang Lin, Yu-Chih Lo, Steven M. Damo and Hao Wu 39. Structure of IFIShf and its Receptors 261 50. Assembly of Signaling Complexes for Mark R. Walter TNF Receptor Family Molecules 347 Gail A. Bishop and Bruce S. Hostager 40. Structure and Function of Tumor Necrosis Factor (TNF) at the Cell 51. Mechanisms of CD40 Signaling the Surface 265 Immune System 353 Hao Wu and Sarah G. Hymowitz Randolph Noelle, Victor C. de Vries and Raul Elgueta 41. The Mechanism of NGF Signaling 52. Role of Lipid Domains in EGF Receptor Suggested by the p75 and TrkA Signaling 359 Receptor Complexes 277 Linda J. Pike J. Fernando Bazan and Christian Wiesmann 53. Lipid-Mediated Localization of Signaling 42. The Mechanism of VEGFR Activation Proteins 365 byVEGF 287 Maurine E. Linder Christian Wiesmann

43. Receptor-Ligand Recognition in the 54. Organization of Photoreceptor Signaling TGF(3 Superfamily as Suggested by Complexes 373 Susan Tsunoda Crystal Structures of their Ectodomain Complexes 293 55. Transmembrane Receptor Matthias K. Dreyer Oligomerization 379 44. Insulin Receptor Complex and Signaling Darren R. Tyson and Ralph A. Bradshaw by Insulin 301 Lindsay G. Sparrow and S. Lance Macaulay VOLUME 3 45. Structure and Mechanism of the Insulin Contributors xxi Receptor Tyrosine Kinase 307 Preface to the Second Edition xliii Stevan R. Hubbard Preface to the First Edition xlv 46. IL-21 Increased Potency Design 315 Kent Bondensgaard, Lishan Kang, and SivA. Hjorth Part III 47. Signaling of IL-4R, a Typical Class I Transcription and Translation: Cytokine Receptor: What Defines the Nuclear and Cytoplasmic Events 1995 Quiescent State? 323 Michael Karin Thomas Weidemann, Siegfried Hofinger, and Manfred Auer Section A - Nuclear Receptors 1997 48. Epidermal Growth Factor Kinases and Michael G. Rosenfeld their Activation in Receptor Mediated Signaling 329 244. Nuclear Receptor Coactivators 1999 Andrew H.A. Clayton Joshua D. Stender and Christopher K. Glass XVI Contents

245. Corepressors in Mediating Repression 256. The Smads 2099 by Nuclear Receptors 2005 Malcolm Whitman Gratien G. Prefontaine, Peter J. Cook and Michael G. Rosenfeld Section C - Damage/Stress Responses 2105 Albert J. Fornace, Jr. 246. Steroid Hormone Receptor Signaling 2015 257. Complexity of Stress Signaling 2107 Vincent Giguere Daniel R. Hyduke, Sally A. Amundson, and Albert J. Fornace, Jr. 247. Role of COUP-TFII in Congenital Diaphragmatic Hernia 2021 258. Signal Transduction in the Escherichia Sumiyasu Ishii, Sophia Y. Tsai and coli SOS Response 2127 Ming-Jer Tsai James J. Foti, Lyle A. Simmons, Penny J. Beuning and Graham C. Walker 248. Nuclear Receptors in Drosophila Melanogaster 2027 259. Oxidative Stress and Free Radical Vincent C. Henrich and Joshua M. Beatty Signal Transduction 2137 Bruce Demple Section B -Transcription Factors 2039 Marc Montminy 260. Screening Approaches to Identify Genes Required for DNA Double- 249. JAK-STAT Signaling 2041 Strand Break Damage Signaling in the Li Song and Christian Schindler Yeast Saccharomyces Cerevisiae 2145 Craig B. Bennett 250. FOXO Transcription Factors: Key Targets of the PI3K-Akt Pathway That 261. Radiation Responses in Regulate Cell Proliferation, Survival, Drosophila 2159 and Organismal Aging 2049 Wan-Jin Lu, Naoko Sogame and John M. Abrams Anne Brunet, Hien Tran, and Michael E. Greenberg 262. Double-strand Break Recognition and its Repair by Non-homologous 251. The Multi-gene Family of Transcription End-Joining 2165 Factor AP-1 2059 Xiaopoing Cui and Michael R. Lieber Peter Angel and Jochen Hess 263. ATM Mediated Signaling Defends the 252. NFK,B: a Key Integrator of Cell Integrity of the Genome 2171 Signaling 2069 Martin F. Lavin, Magtouf Gatei, Philip Chen, John K. Westwick, Klaus Schwamborn, and Amanda Kijas and Sergei Kozlov Frank Mercurio 264. Signaling to the p53 Tumor Suppressor 253. Transcriptional Regulation via the cAMP through Pathways Activated by Responsive Activator CREB 2077 Genotoxic and Non-Genotoxic Paul K. Brindle Stresses 2185 254. The NFAT Family: Structure, Regulation Carl W. Anderson and Ettore Appella and Biological Functions 2083 Fernando Macian, Fernando Cruz-Guilloty, 265. The p53 Master Regulator and Sonia Sharma and Anjana Rao Rules of Engagement with Target Sequences 2205 255. Ubiquitination / Proteasome 2093 Alberto Inga, Jennifer J. Jordan, Daniel Menendez, Daniel Kornitzer and Aaron Ciechanover Veronica De Sanctis and Michael A. Resnick Contents

266. Nuclear and Cytoplasmic Functions of 278. Signaling to Cytoplasmic Abl Tyrosine Kinase 221 7 Polyadenylation and Translation 2317 Jean Y.J.Wang Jong Heon Kim and Joel D. Richter

267. Radiation Induced Cytoplasmic 279. Translational Control in Invertebrate Signaling 2225 Development 2323 Frank-D. Bohmer, Carsten Weiss and Jocelyn Moore and Paul Lasko Peter Herrlich

268. The Heat Shock Response and the 280. The Role of Alternative Splicing During Stress of Misfolded Proteins 2231 the Cell Cycle and Programmed Cell Richard I. Morimoto and Sandy D. Westerheide Death 2329 Xialu Li and James L. Manley 269. Hypoxia Mediated Signaling Pathways 2241 281. Signaling Pathways that Mediate Denise A. Chan, Albert C. Koong, and Translational Control of Ribosome AmatoJ. Giaccia Recruitment to mRNA 2335 Ryan J. O. Dowling and Nahum Sonenberg 270. Regulation of mRNA Turnover by Cellular Stress 2247 Subramanya Srikantan and Myriam Gorospe Section E - Chromatin and its Modification 2343 271. Oncogenic Stress Responses 2257 Jerry L. Workman Dmitry V. Bulavin

272. Ubiquitin and FANC Stress 282. The SWI/SNF and RSC Nucleosome Responses 2265 Remodeling Complexes 2345 Stacy A. Williams and Gary M. Kupfer Nilanjana Chatterjee, Payel Sen, and Blaine Bartholomew 273. Stress and 1-H2AX 2273 Jennifer S. Dickey, Christophe E. Redon, 283. ISWI Chromatin Remodeling Asako J. Nakamura, Brandon J. Baird, Complexes 2357 Olga A. Sedelnikova, and William M. Bonner Toshio Tsukiyama, Naomi Bogenschutz, Tracey Kwong, Jairo Rodriguez, Ashwin Unnikrishnan, and Adam Yadon Section D - Post-transcriptional Control 2283 284. The INO80 Chromatin Remodeling NahumSonenberg Complex 2363 274. Translational Control by Amino Acids Mingming Chen and Xuetong Shen and Energy 2285 Kathrin Thedieck and Michael N. Hall 285. Histone Acetylation Complexes 2369 Tara L. Burke and Patrick A. Grant 275. Translation Control and Insulin 286. Regulation of Histone Deacetylase Signaling 2295 Anand Selvaraj and George Thomas Activities and Functions by Phosphorylation and 276. ERand oxidative stress: Implications in Dephosphorylation 2379 disease 2301 Edward Seto and Xiang-Jiao Yang Jyoti D. Malhotra and Randal J. Kaufman 287. Histone Methylation: Chemically 277. Regulation of mRNA Turnover 2311 Inert But Chromatin Dynamic 2389 Ann-Bin Shyu and Chyi-Ying A. Chen Johnathan R. Whetstine Contents

288. Histone Phosphorylation: 297. Mitochondrial Dynamics: Fusion and Chromatin Modifications that Link Division 2499 Cell Signaling Pathways to Nuclear Yasushi Tamura, Miho lijima and Hiromi Sesaki Function Regulation 2399 Priscilla Nga leng Lau and Peter Cheung 298. The SREBP Pathway: Gene Regulation through Sterol Sensing and Gated Protein Trafficking 2505 289. Histone Variants: Signaling or Arun Radhakrishnan, Li-Ping Sun, Structural Modules? 2409 Peter J. Espenshade, Joseph L. Goldstein and Toyotaka Ishibashi, Andra Li and Juan Ausio Michael S. Brown

290. Silent Chromatin Formation and 299. Regulating Endoplasmic Reticulum Regulation in the Yeast Function through the Unfolded Protein Saccharomyces cerevisiae 2427 Response 2511 Melissa R. Koch and Lorraine Pillus Alicia A. Bicknell and Maho Niwa

291. Gene Silencing and Chromatin 300. Signaling Pathways from Mitochondria Modification by Polycomb to the Cytoplasm and Nucleus 2527 Complexes in Flies and Immo E. Scheffler Humans 2437 301. Apoptosis Signaling: A Means to Jeffrey A. Simon an End 2535 Lisa}. Pagliari, Michael J. Pinkoski, and 292. Histone Ubiquitination 2449 Douglas R. Green Vikki M. Weake and Jerry L. Workman 302. Regulation of Cell Cycle 293. Chromatin Mediated Control of Gene Progression 2545 Expression in Innate Immunity and Jennifer Scorah, and Claire H. McGowan Inflammation 2461 Gioacchino Natoli 303. Signaling During Organelle Division and Inheritance: Peroxisomes 2555 Andrei D. Fagarasanu and Richard A. Rachubinski Part IV Signaling from Intracellular 304. Signaling at the Nuclear Envelope 2563 Compartments 2467 Geza Ambrus and Larry Gerace Marilyn C. Farquhar and Suresh 305. Bidirectional Crosstalk between Actin Subramani Dynamics and Endocytosis 2571 Giorgio Scita and Pier Paolo Di Fiore

294. Protein Quality Control in the 306. Signaling in Autophagy Related Endoplasmic Reticulum 2471 Pathways 2583 Yuki Okuda-Shimizu, Ying Shen, and Patrice Codogno and Alfred J. Meijer Linda Hendershot

295. Quality Control and Quality Assurance PartV in the Mitochondrion 2477 Cell-Cell and Cell-Matrix Carolyn K. Suzuki Interaction 2589 E. Brad Thompson 296. Protein Quality Control in Peroxisomes: Ubiquitination of the Peroxisomal 307. Overview of Cell-Cell and Cell-Matrix Targeting Signal Receptors 2489 Interactions 2591 Chris Williams and Ben Distel E. Brad Thompson and Ralph A. Bradshaw Contents

308. Interactive Signaling Pathways in the 319. Cytokines and Cytokine Receptors Vasculature 2593 Regulating Cell Survival, Igor Prudovsky, Volkhard Lindner, Calvin Vary and Proliferation, and Differentiation in Robert E. Friesel Hematopoiesis 2733 Fiona J. Pixley and E. Richard Stanley 309. Signaling Pathways Involved in Cardiogenesis 2601 320. Signaling Pathways Regulating Growth Deepak Srivastava and Chulan Kwon and Differentiation of Adult Stem Cells 2743 Larry Denner, Margaret Howe and 310. Regulatory Signaling in Pancreatic Randall J. Urban Organogenesis: Implications for Aberrant Signaling in Pancreatic 321. In Vivo Imaging of Cellular Network Cancer 2611 Signaling 2753 Catherine Carriere and Murray Korc Werner Gobel, Bjorn M. Kampa and Fritjof Helmchen 311. Trophic Effects of Gut Hormones in the Gastrointestinal Tract 2621 Part VI Kanika A. Bowen and B. Mark Evers Disease Pathophysiology: 312. The Neurotrophin Factors 2631 Translational Implications 2759 J. ReginoPerez-Polo Murray Korc

313. Cell to Cell and Cell-Matrix 322. The Roles of Ras Family Small GTPases Interactions in Bone 2647 in Breast Cancer 2763 Ariella B. Hanker and ChanningJ. Der Lynda F. Bonewald 323. Translational Implications of Stromal- 314. Cell-Cell Signaling in the Testis and Epithelial Interactions in Prostate Ovary 2663 Cancer and the Potential Role of Michael K. Skinner, Eric E. Nilsson and Prostate Cancer Stem/Progenitor Ramji K. Bhandari Cells 2773 Sophia L. Maund and Scott D. Cramer 315. Signal Transduction in T Lymphocytes 2679 324. Aberrant Signaling Pathways in RolfKonig Pancreatic Cancer: Opportunities for Targeted Therapeutics 2783 316. Signal Transduction via the B Cell Alixanna Norris and Murray Korc Antigen Receptor: A Crucial Regulator of B Cell Biology 2689 325. The Evolution and Maintenance Louis B. Justement of the Multiple Myeloma Cell Clone within the Liquid Bone 317. Signaling Pathways in the Normal and Marrow Compartment: Therapeutic Neoplastic Breast 2699 Implications 2799 Tushar B. Deb, Danica Ramljak, Klaus Podar and Kenneth C. Anderson Robert B. Dickson2, Michael D. Johnson, and Robert Clarke 326. The Pathophysiologic Role of the Bone 318. Kidney 2707 Marrow Environment and its Niches in William J. Arendshorst and Elsa Multiple Myeloma 2811 Bello-Reuss Klaus Podar and Kenneth C. Anderson Contents

327. Signaling Targets in Myeloid 334. CXC Chemokine Signaling in Interstitial Leukemias 2821 Lung Diseases 2907 Muneyoshi Futami and Seth J. Corey Robert M. Strieter and Borna Mehrad

328. Signaling Targets in Lymphoid 335. Systemic Sclerosis 2913 Leukemias 2831 Carol A. Feghali-Bostwick, and John Varga Muneyoshi Futami and Seth J. Corey 336. Signal Transduction in Rheumatoid Arthritis and Systemic Lupus 329. Targeting Ras for Anticancer Drug Erythematosus 2919 Discovery 2837 Thomas Dorner, and Peter E. Lipsky Jen Jen Yeh, James P. Madigan, Paul M. Campbell, Patrick J. Roberts, Lanika DeGraffenreid and ChanningJ. Der 337. Translational Concepts in Vasculitis 2933 Daniel A. Albert and David B. Talmadge 330. Targeting EWS/FLI1 Driven Signaling Pathways as Therapy for Tumors of the 338. Advances in Understanding the Ewing's Sarcoma Family 2859 Pathogenesis of Inflammatory Bowel Vicente Notario, Silvia Mateo-Lozano, Joaqufn Villar, and Oscar M. Tirado Disease 2945 David S. Kotlyar, Wojciech C. Blonski, and Gary R. Lichtenstein 331. IRS-Protein Scaffolds and Insulin/ IGF Action in Central and Peripheral 339. Translational Implications of Tissues 2873 Proteomics 2959 Morris F. White Sam Hanash

332. Adipokine Signaling: Implications for 340. Translational Implications of Obesity 2885 microRNAs in Clinical Diagnostics and Rexford S. Ahima and Gladys M. Varela Therapeutics 2965 333. Angiogenesis Signaling Pathways as Lorenzo F. Sempere and Sakari Kauppinen Targets in Cancer Therapy 2895 Index 2983 Chery A. Whipple and Murray Korc