The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B

Immunological Reviews

Volumn 232, Issue 1, 2009, Pages 240-254

  Lapinski, Philip E ^a   Oliver, Jennifer A ^a   Bodie, Jennifer N ^a   Marti, Francesc ^a   King, Philip D ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Adapter proteins; Autoimmunity; Knockout mice; Protein tyrosine kinases; Signal transduction; T lymphocytes

Indexed keywords

ADAPTOR PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN ALX; PROTEIN SH2; PROTEIN SH2D4A; PROTEIN SH2D4B; T CELL SPECIFIC ADAPTER PROTEIN; UNCLASSIFIED DRUG;

ANGIOGENESIS; AUTOIMMUNE DISEASE; DISEASE PREDISPOSITION; ENZYME ACTIVATION; ENZYME ACTIVITY; HUMAN; LYMPHOCYTE MIGRATION; NONHUMAN; NUCLEAR IMPORT; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; HUMANS; MEMBRANE PROTEINS; MICE; PROTEIN MULTIMERIZATION; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 70350413774     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2009.00829.x     Document Type: Review

References (95)

1. Samelson LE. Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol 2002 20 : 371 394.
2. Lindquist JA, Simeoni L, Schraven B. Transmembrane adapters: attractants for cytoplasmic effectors. Immunol Rev 2003 191 : 165 182.
3. Simeoni L, Kliche S, Lindquist J, Schraven B. Adaptors and linkers in T and B cells. Curr Opin Immunol 2004 16 : 304 313.
4. Liu SK, Berry DM, McGlade CJ. The role of Gads in hematopoietic cell signalling. Oncogene 2001 20 : 6284 6290.
5. Tari AM, Lopez-Berestein G. GRB2: a pivotal protein in signal transduction. Semin Oncol 2001 28 : 142 147.
6. Peterson EJ. The TCR ADAPts to integrin-mediated cell adhesion. Immunol Rev 2003 192 : 113 121.
7. Sommers CL, Samelson LE, Love PE. LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways. BioEssays 2004 26 : 61 67.
8. Wu JN, Koretzky GA. The SLP-76 family of adapter proteins. Semin Immunol 2004 16 : 379 393.
9. Liu BA, Jablonowski K, Raina M, Arce M, Pawson T, Nash PD. The human and mouse complement of SH2 domain proteins - establishing the boundaries of phosphotyrosine signaling. Mol Cell 2006 22 : 851 868.
10. Spurkland A, et al. Molecular cloning of a T cell-specific adapter protein (TSAd) containing an Src homology (SH) 2 domain and putative SH3 and phosphotyrosine binding sites. J Biol Chem 1998 273 : 4539 4546.
11. Kuriyan J, Cowburn D. Modular peptide recognition domains in eukaryotic signaling. Annu Rev Biophys Biomol Struct 1997 26 : 259 288.
12. Sundvold V, et al. T cell-specific adapter protein inhibits T cell activation by modulating Lck activity. J Immunol 2000 165 : 2927 2931.
13. Dai KZ, et al. Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5′-monophosphate-responsive element in the proximal SH2D2A promoter. J Immunol 2004 172 : 6144 6151.
14. Kolltveit KM, et al. Expression of SH2D2A in T-cells is regulated both at the transcriptional and translational level. Mol Immunol 2008 45 : 2380 2390.
15. Choi YB, Kim CK, Yun Y. Lad, an adapter protein interacting with the SH2 domain of p56lck, is required for T cell activation. J Immunol 1999 163 : 5242 5249.
16. Rajagopal K, et al. RIBP, a novel Rlk/ Txk- and itk-binding adaptor protein that regulates T cell activation. J Exp Med 1999 190 : 1657 1668.
17. Marti F, Garcia GG, Lapinski PE, MacGregor JN, King PD. Essential role of the T cell-specific adapter protein in the activation of LCK in peripheral T cells. J Exp Med 2006 203 : 281 287.
18. Matsumoto T, et al. VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. EMBO J 2005 24 : 2342 2353.
19. Park D, Choi YB, Han MK, Kim UH, Shin J, Yun Y. Adaptor protein Lad relays PDGF signal to Grb2 in lung cells: a tissue-specific PDGF signal transduction. Biochem Biophys Res Commun 2001 284 : 275 281.
20. Perchonock CE, Pajerowski AG, Nguyen C, Shapiro MJ, Shapiro VS. The related adaptors, adaptor in lymphocytes of unknown function X and Rlk/Itk-binding protein, have nonredundant functions in lymphocytes. J Immunol 2007 179 : 1768 1775.
21. Oda T, Muramatsu MA, Isogai T, Masuho Y, Asano S, Yamashita T. HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells. Biochem Biophys Res Commun 2001 288 : 1078 1086.
22. Greene TA, Powell P, Nzerem C, Shapiro MJ, Shapiro VS. Cloning and characterization of ALX, an adaptor downstream of CD28. J Biol Chem 2003 278 : 45128 45134.
23. Herrin BR, Groeger AL, Justement LB. The adaptor protein HSH2 attenuates apoptosis in response to ligation of the B cell antigen receptor complex on the B lymphoma cell line, WEHI-231. J Biol Chem 2005 280 : 3507 3515.
24. Herrin BR, Justement LB. Expression of the adaptor protein hematopoietic Src homology 2 is up-regulated in response to stimuli that promote survival and differentiation of B cells. J Immunol 2006 176 : 4163 4172.
25. Lapinski PE, Oliver JA, Kamen LA, Hughes ED, Saunders TL, King PD. Genetic analysis of SH2D4A, a novel adapter protein related to T cell-specific adapter and adapter protein in lymphocytes of unknown function, reveals a redundant function in T cells. J Immunol 2008 181 : 2019 2027.
26. Patrakka J, et al. Expression and subcellular distribution of novel glomerulus-associated proteins dendrin, ehd3, sh2d4a, plekhh2, and 2310066E14Rik. J Am Soc Nephrol 2007 18 : 689 697.
27. Marti F, Post NH, Chan E, King PD. A transcription function for the T cell-specific adapter (TSAd) protein in T cells: critical role of the TSAd Src homology 2 domain. J Exp Med 2001 193 : 1425 1430.
28. Palacios EH, Weiss A. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene 2004 23 : 7990 8000.
29. Sundvold-Gjerstad V, et al. The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity. Eur J Immunol 2005 35 : 1612 1620.
30. Granum S, et al. Structure function analysis of SH2D2A isoforms expressed in T cells reveals a crucial role for the proline rich region encoded by SH2D2A exon 7. BMC Immunol 2006 7 : 15.
31. Granum S, et al. Modulation of Lck function through multisite docking to T cell-specific adapter protein. J Biol Chem 2008 283 : 21909 21919.
32. Marti F, King PD. The p95-100 kDa ligand of the T cell-specific adaptor (TSAd) protein Src-homology-2 (SH2) domain implicated in TSAd nuclear import is p97 Valosin-containing protein (VCP). Immunol Lett 2005 97 : 235 243.
33. Woodman PG. p97, a protein coping with multiple identities. J Cell Sci 2003 116 : 4283 4290.
34. Wang Q, Song C, Li CC. Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions. J Struct Biol 2004 146 : 44 57.
35. Meyer HH, Shorter JG, Seemann J, Pappin D, Warren G. A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. EMBO J 2000 19 : 2181 2192.
36. Dai RM, Li CC. Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation. Nat Cell Biol 2001 3 : 740 744.
37. Ye Y, Meyer HH, Rapoport TA. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature 2001 414 : 652 656.
38. Jarosch E, Geiss-Friedlander R, Meusser B, Walter J, Sommer T. Protein dislocation from the endoplasmic reticulum - pulling out the suspect. Traffic 2002 3 : 530 556.
39. Dai RM, Chen E, Longo DL, Gorbea CM, Li CC. Involvement of valosin-containing protein, an ATPase co-purified with IκBα and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IκBα. J Biol Chem 1998 273 : 3562 3573.
40. Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S. Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 2001 107 : 667 677.
41. Shcherbik N, Zoladek T, Nickels JT, Haines DS. Rsp5p is required for ER bound Mga2p120 polyubiquitination and release of the processed/tethered transactivator Mga2p90. Curr Biol 2003 13 : 1227 1233.
42. Egerton M, Ashe OR, Chen D, Druker BJ, Burgess WH, Samelson LE. VCP, the mammalian homolog of cdc48, is tyrosine phosphorylated in response to T cell antigen receptor activation. EMBO J 1992 11 : 3533 3540.
43. Egerton M, Samelson LE. Biochemical characterization of valosin-containing protein, a protein tyrosine kinase substrate in hematopoietic cells. J Biol Chem 1994 269 : 11435 11441.
44. Madeo F, Schlauer J, Zischka H, Mecke D, Frohlich KU. Tyrosine phosphorylation regulates cell cycle-dependent nuclear localization of Cdc48p. Mol Biol Cell 1998 9 : 131 141.
45. Lapinski PE, MacGregor JN, Marti F, King PD. The T cell-specific adapter protein functions as regulator of peripheral but not central immunological tolerance. Adv Exp Med Biol 2006 584 : 73 88.
46. Drappa J, et al. Impaired T cell death and lupus-like autoimmunity in T cell-specific adapter protein-deficient mice. J Exp Med 2003 198 : 809 821.
47. Yamaguchi H, Hendrickson WA. Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature 1996 384 : 484 489.
48. Xu W, Doshi A, Lei M, Eck MJ, Harrison SC. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell 1999 3 : 629 638.
49. Hermiston ML, Xu Z, Weiss A. CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol 2003 21 : 107 137.
50. Dykstra M, Cherukuri A, Sohn HW, Tzeng SJ, Pierce SK. Location is everything: lipid rafts and immune cell signaling. Annu Rev Immunol 2003 21 : 457 481.
51. Horejsi V. The roles of membrane microdomains (rafts) in T cell activation. Immunol Rev 2003 191 : 148 164.
52. Filipp D, Julius M. Lipid rafts: resolution of the "fyn problem"? Mol Immunol 2004 41 : 645 656.
53. Filipp D, Leung BL, Zhang J, Veillette A, Julius M. Enrichment of lck in lipid rafts regulates colocalized fyn activation and the initiation of proximal signals through TCR alpha beta. J Immunol 2004 172 : 4266 4274.
54. Brdicka T, et al. Phosphoprotein associated with glycosphingolipid- enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J Exp Med 2000 191 : 1591 1604.
55. Kawabuchi M, et al. Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature 2000 404 : 999 1003.
56. Veillette A, Latour S, Davidson D. Negative regulation of immunoreceptor signaling. Annu Rev Immunol 2002 20 : 669 707.
57. Park D, Park I, Lee D, Choi YB, Lee H, Yun Y. The adaptor protein Lad associates with the G protein beta subunit and mediates chemokine-dependent T-cell migration. Blood 2007 109 : 5122 5128.
58. Inngjerdingen M, Torgersen KM, Maghazachi AA. Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis. Blood 2002 99 : 4318 4325.
59. Ottoson NC, Pribila JT, Chan AS, Shimizu Y. Cutting edge: T cell migration regulated by CXCR4 chemokine receptor signaling to ZAP-70 tyrosine kinase. J Immunol 2001 167 : 1857 1861.
60. Ticchioni M, et al. Signaling through ZAP-70 is required for CXCL12-mediated T-cell transendothelial migration. Blood 2002 99 : 3111 3118.
61. Marti F, Lapinski PE, King PD. The emerging role of the T cell-specific adaptor (TSAd) protein as an autoimmune disease-regulator in mouse and man. Immunol Lett 2005 97 : 165 170.
62. King PD. Lupus-like autoimmunity caused by defects in T-cell signal transduction. Curr Opin Investig Drugs 2004 5 : 517 523.
63. Willerford DM, Chen J, Ferry JA, Davidson L, Ma A, Alt FW. Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartment. Immunity 1995 3 : 521 530.
64. Kneitz B, Herrmann T, Yonehara S, Schimpl A. Normal clonal expansion but impaired Fas-mediated cell death and anergy induction in interleukin-2-deficient mice. Eur J Immunol 1995 25 : 2572 2577.
65. Li XC, et al. IL-15 and IL-2: a matter of life and death for T cells in vivo. Nat Med 2001 7 : 114 118.
66. Bayer AL, Yu A, Adeegbe D, Malek TR. Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period. J Exp Med 2005 201 : 769 777.
67. Fontenot J, Rasmussen J, Gavin M, Rudensky A. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 2005 6 : 1142 1151.
68. Furtado GC, Curotto de Lafaille MA, Kutchukhidze N, Lafaille JJ. Interleukin 2 signaling is required for CD4(+) regulatory T cell function. J Exp Med 2002 196 : 851 857.
69. Maloy K, Powrie F. Fueling regulation: IL-2 keeps CD4+ Treg cells fit. Nat Immunol 2005 6 : 1071 1072.
70. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 2005 201 : 723 735.
71. Thornton AM, Donovan EE, Piccirillo CA, Shevach EM. Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J Immunol 2004 172 : 6519 6523.
72. Dai KZ, et al. The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis. Genes Immun 2001 2 : 263 268.
73. Lorentzen AR, et al. The SH2D2A gene and susceptibility to multiple sclerosis. J Neuroimmunol 2008 197 : 152 158.
74. Smerdel A, et al. Genetic association between juvenile rheumatoid arthritis and polymorphism in the SH2D2A gene. Genes Immun 2004 5 : 310 312.
75. Notturno F, Pace M, De Angelis MV, Caporale CM, Giovannini A, Uncini A. Susceptibility to chronic inflammatory demyelinating polyradiculoneuropathy is associated to polymorphic GA repeat in the SH2D2A gene. J Neuroimmunol 2008 197 : 124 127.
76. Shapiro MJ, Powell P, Ndubuizu A, Nzerem C, Shapiro VS. The ALX Src homology 2 domain is both necessary and sufficient to inhibit T cell receptor/ CD28-mediated up-regulation of RE/AP. J Biol Chem 2004 279 : 40647 40652.
77. Shapiro MJ, Chen YY, Shapiro VS. The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation. J Biol Chem 2005 280 : 38242 38246.
78. Perchonock CE, et al. Negative regulation of interleukin-2 and p38 mitogen-activated protein kinase during T-cell activation by the adaptor ALX. Mol Cell Biol 2006 26 : 6005 6015.
79. Zhu M, Janssen E, Leung K, Zhang W. Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. J Biol Chem 2002 277 : 46151 46158.
80. Zhu M, et al. Negative regulation of lymphocyte activation by the adaptor protein LAX. J Immunol 2005 174 : 5612 5619.
81. Shapiro MJ, Nguyen CT, Aghajanian H, Zhang W, Shapiro VS. Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms. J Immunol 2008 181 : 7055 7061.
82. Kitamura D, Kaneko H, Miyagoe Y, Ariyasu T, Watanabe T. Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage. Nucleic Acids Res 1989 17 : 9367 9379.
83. Zhan X, Hu X, Hampton B, Burgess WH, Friesel R, Maciag T. Murine cortactin is phosphorylated in response to fibroblast growth factor-1 on tyrosine residues late in the G1 phase of the BALB/c 3T3 cell cycle. J Biol Chem 1993 268 : 24427 24431.
84. Ensenat D, et al. A novel src homology 3 domain-containing adaptor protein, HIP-55, that interacts with hematopoietic progenitor kinase 1. J Biol Chem 1999 274 : 33945 33950.
85. Sparks AB, Hoffman NG, McConnell SJ, Fowlkes DM, Kay BK. Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins. Nat Biotechnol 1996 14 : 741 744.
86. Gomez TS, et al. HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse. Immunity 2006 24 : 741 752.
87. Han J, Shui JW, Zhang X, Zheng B, Han S, Tan TH. HIP-55 is important for T-cell proliferation, cytokine production, and immune responses. Mol Cell Biol 2005 25 : 6869 6878.
88. Taniuchi I, Kitamura D, Maekawa Y, Fukuda T, Kishi H, Watanabe T. Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptor- coupled tyrosine kinases. EMBO J 1995 14 : 3664 3678.
89. Wu LW, et al. VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor. J Biol Chem 2000 275 : 6059 6062.
90. Park D, Yun Y. Tyrosine phosphorylation-dependent yeast two-hybrid system for the identification of the SH2 domain-binding proteins. Mol Cell 2001 12 : 244 249.
91. Sun W, et al. MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway. J Biol Chem 2001 276 : 5093 5100.
92. Sun W, et al. MEK kinase 2 and the adaptor protein Lad regulate extracellular signal-regulated kinase 5 activation by epidermal growth factor via Src. Mol Cell Biol 2003 23 : 2298 2308.
93. Richard KC, Bertolesi GE, Dunfield LD, McMaster CR, Nachtigal MW. TSAd interacts with Smad2 and Smad3. Biochem Biophys Res Commun 2006 347 : 266 272.
94. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006 7 : 359 371.
95. Frame MC. Newest findings on the oldest oncogene; how activated src does it. J Cell Sci 2004 117 : 989 998.