DOI QR코드

DOI QR Code

The Role of SH2 Domain-containing Leukocyte Phosphoprotein of 76 kDa in the Regulation of Immune Cell Development and Function

  • Koretzky, Gary A. (Department of Pathology and Laboratory Medicine and Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine)
  • Received : 2009.05.06
  • Accepted : 2009.05.14
  • Published : 2009.06.30

Abstract

Recent years have seen an explosion of new knowledge defining the molecular events that are critical for development and activation of immune cells. Much of this new information has come from a careful molecular dissection of key signal transduction pathways that are initiated when immune cell receptors are engaged. In addition to the receptors themselves and critical effector molecules, these signaling pathways depend on adapters, proteins that have no intrinsic effector function but serve instead as scaffolds to nucleate multimolecular complexes. This review summarizes some of what has been learned about one such adapter protein, SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76), and how it regulates and integrates signals after engagement of immunoreceptors and integrins on various immune cell lineages.

Keywords

References

  1. Smith-Garvin JE, Koretzky GA, Jordan MS: T Cell activation. Annu Rev Immunol 27;591-619, 2009 https://doi.org/10.1146/annurev.immunol.021908.132706
  2. June CH, Fletcher MC, Ledbetter JA, Schieven GL, Siegel JN, Phillips AF, Samelson LE: Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. Proc Natl Acad Sci U S A 87;7722-7726, 1990 https://doi.org/10.1073/pnas.87.19.7722
  3. Iwashima M, Irving BA, van Oers NS, Chan AC, Weiss A: Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science 263;1136-1139, 1994 https://doi.org/10.1126/science.7509083
  4. Koretzky GA, Abtahian F, Silverman MA: SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond. Nat Rev Immunol 6;67-78, 2006 https://doi.org/10.1038/nri1750
  5. Jackman JK, Motto DG, Sun Q, Tanemoto M, Turck CW, Peltz GA, Koretzky GA, Findell PR: Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. J Biol Chem 270;7029-7032, 1995 https://doi.org/10.1074/jbc.270.13.7029
  6. Clements JL, Ross-Barta SE, Tygrett LT, Waldschmidt TJ, Koretzky GA: SLP-76 expression is restricted to hemopoietic cells of monocyte, granulocyte, and T lymphocyte lineage and is regulated during T cell maturation and activation. J Immunol 161;3880-3889, 1998
  7. Bubeck Wardenburg J, Pappu R, Bu JY, Mayer B, Chernoff J, Straus D, Chan AC: Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity 9;607-616, 1998 https://doi.org/10.1016/S1074-7613(00)80658-5
  8. Onodera H, Motto DG, Koretzky GA, Rothstein DM: Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase. J Biol Chem 271;22225-22230, 1996 https://doi.org/10.1074/jbc.271.36.22225
  9. Raab M, da Silva AJ, Findell PR, Rudd CE: Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/ CD3 induction of interleukin-2. Immunity 6;155-164, 1997 https://doi.org/10.1016/S1074-7613(00)80422-7
  10. Tuosto L, Michel F, Acuto O: p95vav associates with tyrosine- phosphorylated SLP-76 in antigen-stimulated T cells. J Exp Med 184;1161-1166, 1996 https://doi.org/10.1084/jem.184.3.1161
  11. Wu J, Motto DG, Koretzky GA, Weiss A: Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity 4;593-602, 1996 https://doi.org/10.1016/S1074-7613(00)80485-9
  12. Wunderlich L, Farago A, Downward J, Buday L: Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes. Eur J Immunol 29;1068-1075, 1999 https://doi.org/10.1002/(SICI)1521-4141(199904)29:04<1068::AID-IMMU1068>3.0.CO;2-P
  13. Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ: Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. J Biol Chem 275;2219-2230, 2000 https://doi.org/10.1074/jbc.275.3.2219
  14. Su YW, Zhang Y, Schweikert J, Koretzky GA, Reth M, Wienands J: Interaction of SLP adaptors with the SH2 domain of Tec family kinases. Eur J Immunol 29;3702-3711, 1999 https://doi.org/10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R
  15. Yablonski D, Kadlecek T, Weiss A: Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT. Mol Cell Biol 21;4208-4218, 2001 https://doi.org/10.1128/MCB.21.13.4208-4218.2001
  16. Liu Q, Berry D, Nash P, Pawson T, McGlade CJ, Li SS: Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition. Mol Cell 11;471-481, 2003 https://doi.org/10.1016/S1097-2765(03)00046-7
  17. Liu SK, Fang N, Koretzky GA, McGlade CJ: The hematopoietic- specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Curr Biol 9;67-75, 1999 https://doi.org/10.1016/S0960-9822(99)80017-7
  18. Seet BT, Berry DM, Maltzman JS, Shabason J, Raina M, Koretzky GA, McGlade CJ, Pawson T: Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif. EmboJ 26;678-689, 2007
  19. Sauer K, Liou J, Singh SB, Yablonski D, Weiss A, Perlmutter RM: Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes. J Biol Chem 276; 45207-45216, 2001 https://doi.org/10.1074/jbc.M106811200
  20. da Silva AJ, Li Z, de Vera C, Canto E, Findell P, Rudd CE: Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production. Proc Natl Acad Sci U S A 94;7493-7498, 1997 https://doi.org/10.1073/pnas.94.14.7493
  21. Musci MA, Hendricks-Taylor LR, Motto DG, Paskind M, Kamens J, Turck CW, Koretzky GA: Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases. J Bio Chem 272;11674-11677, 1997 https://doi.org/10.1074/jbc.272.18.11674
  22. Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ, Barr VA, Samelson LE: T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol 158;1263-1275, 2002 https://doi.org/10.1083/jcb.200203043
  23. Samelson LE: Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol 20;371-394, 2002 https://doi.org/10.1146/annurev.immunol.20.092601.111357
  24. Motto DG, Ross SE, Wu J, Hendricks-Taylor LR, Koretzky GA: Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production. J Exp Med 183;1937-1943, 1996 https://doi.org/10.1084/jem.183.4.1937
  25. Yablonski D, Kuhne MR, Kadlecek T, Weiss A: Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell. Science 281;413-416, 1998 https://doi.org/10.1126/science.281.5375.413
  26. Clements JL, Yang B, Ross-Barta SE, Eliason SL, Hrstka RF, Williamson RA, Koretzky GA: Requirement for the leukocyte- specific adapter protein SLP-76 for normal T cell development. Science 281;416-419, 1998 https://doi.org/10.1126/science.281.5375.416
  27. Pivniouk V, Tsitsikov E, Swinton P, Rathbun G, Alt FW, Geha RS: Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76. Cell 94;229-238, 1998 https://doi.org/10.1016/S0092-8674(00)81422-1
  28. Maltzman JS, Kovoor L, Clements JL, Koretzky GA: Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection. J Exp Med 202;893-900, 2005 https://doi.org/10.1084/jem.20051128
  29. Newbrough SA, Mocsai A, Clemens RA, Wu JN, Silverman MA, Singer AL, Lowell CA, Koretzky GA: SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils. Immunity 19;761-769, 2003 https://doi.org/10.1016/S1074-7613(03)00305-4
  30. Pivniouk VI, Martin TR, Lu-Kuo JM, Katz HR, Oettgen HC, Geha RS: SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells. J Clin Invest 103;1737-1743, 1999
  31. Kettner A, Pivniouk V, Kumar L, Falet H, Lee JS, Mulligan R, Geha RS: Structural requirements of SLP-76 in signaling via the high-affinity immunoglobulin E receptor (Fc epsilon RI) in mast cells. Mol Cell Biol 23;2395-2406, 2003 https://doi.org/10.1128/MCB.23.7.2395-2406.2003
  32. Judd BA, Myung PS, Obergfell A, Myers EE, Cheng AM, Watson SP, Pear WS, Allman D, Shattil SJ, Koretzky GA: Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. J Exp Med 195;705-717, 2002 https://doi.org/10.1084/jem.20011583
  33. Judd BA, Myung PS, Leng L, Obergfell A, Pear WS, Shattil SJ, Koretzky GA: Hematopoietic reconstitution of SLP-76 corrects hemostasis and platelet signaling through alpha IIb beta 3 and collagen receptors. Proc Natl Acad Sci U S A 97;12056-12061, 2000 https://doi.org/10.1073/pnas.97.22.12056
  34. Abtahian F, Guerriero A, Sebzda E, Lu MM, Zhou R, Mocsai A, Myers EE, Huang B, Jackson DG, Ferrari VA, Tybulewicz V, Lowell CA, Lepore JJ, Koretzky GA, Kahn ML: Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299;247-251, 2003 https://doi.org/10.1126/science.1079477
  35. Sebzda E, Hibbard C, Sweeney S, Abtahian F, Bezman N, Clemens G, Maltzman JS, Cheng L, Liu F, Turner M, Tybulewicz V, Koretzky GA, Kahn ML: Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev Cell 11;349-361, 2006 https://doi.org/10.1016/j.devcel.2006.07.007
  36. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 92;83-92, 1998 https://doi.org/10.1016/S0092-8674(00)80901-0
  37. Di Bartolo V, Montagne B, Salek M, Jungwirth B, Carrette F, Fourtane J, Sol-Foulon N, Michel F, Schwartz O, Lehmann WD, Acuto O: A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76. J Exp Med 204;681-691, 2007 https://doi.org/10.1084/jem.20062066
  38. Finco TS, Kadlecek T, Zhang W, Samelson LE, Weiss A: LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway. Immunity 9;617-626, 1998 https://doi.org/10.1016/S1074-7613(00)80659-7
  39. Boerth NJ, Sadler JJ, Bauer DE, Clements JL, Gheith SM, Koretzky GA: Recruitment of SLP-76 to the membrane and glycolipid-enriched membrane microdomains replaces the requirement for linker for activation of T cells in T cell receptor signaling. J Exp Med 192;1047-1058, 2000 https://doi.org/10.1084/jem.192.7.1047
  40. Silverman MA, Shoag J, Wu J, Koretzky GA: Disruption of SLP-76 interaction with Gads inhibits dynamic clustering of SLP-76 and FcepsilonRI signaling in mast cells. Mol Cell Biol 26;1826-1838, 2006 https://doi.org/10.1128/MCB.26.5.1826-1838.2006
  41. Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin ML, Saito T: Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 6;1253-1262, 2005 https://doi.org/10.1038/ni1272
  42. Bezman N, Koretzky GA: Compartmentalization of ITAM and integrin signaling by adapter molecules. Immunol Rev 218;9-28, 2007 https://doi.org/10.1111/j.1600-065X.2007.00541.x
  43. Fuller CL, Braciale VL, Samelson LE: All roads lead to actin: the intimate relationship between TCR signaling and the cytoskeleton. Immunol Rev 191;220-236, 2003 https://doi.org/10.1034/j.1600-065X.2003.00004.x
  44. Jordan MS, Maltzman JS, Kliche S, Shabason J, Smith JE, Obstfeld A, Schraven B, Koretzky GA: In vivo disruption of T cell development by expression of a dominant-negative polypeptide designed to abolish the SLP-76/Gads interaction. Eur J Immunol 37;2961-2972, 2007 https://doi.org/10.1002/eji.200636855
  45. Myung PS, Derimanov GS, Jordan MS, Punt JA, Liu QH, Judd BA, Meyers EE, Sigmund CD, Freedman BD, Koretzky GA: Differential requirement for SLP-76 domains in T cell development and function. Immunity 15;1011-1026, 2001 https://doi.org/10.1016/S1074-7613(01)00253-9
  46. Abtahian F, Bezman N, Clemens R, Sebzda E, Cheng L, Shattil SJ, Kahn ML, Koretzky GA: Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Mol Cell Biol 26;6936-6949, 2006 https://doi.org/10.1128/MCB.01040-06
  47. Kumar L, Pivniouk V, de la Fuente MA, Laouini D, Geha RS: Differential role of SLP-76 domains in T cell development and function. Proc Natl Acad Sci U S A 99;884-889, 2002 https://doi.org/10.1073/pnas.022619199
  48. Wu JN, Jordan MS, Silverman MA, Peterson EJ, Koretzky GA: Differential requirement for adapter proteins Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and adhesion- and degranulation-promoting adapter protein in FcepsilonRI signaling and mast cell function. J Immunol 172;6768-6774, 2004 https://doi.org/10.4049/jimmunol.172.11.6768
  49. Takagi J, Springer TA: Integrin activation and structural rearrangement. Immunol Rev 186;141-163, 2002 https://doi.org/10.1034/j.1600-065X.2002.18613.x
  50. Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B: Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes. J Biol Chem 272; 16077-16080, 1997 https://doi.org/10.1074/jbc.272.26.16077
  51. Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, Zhao H, Schraven B, Koretzky GA: Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130. J Biol Chem 273;25789-25795, 1998 https://doi.org/10.1074/jbc.273.40.25789
  52. Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL: Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells. J Biol Chem 280;23576-23583, 2005 https://doi.org/10.1074/jbc.M413201200
  53. Griffiths EK, Krawczyk C, Kong YY, Raab M, Hyduk SJ, Bouchard D, Chan VS, Kozieradzki I, Oliveira-Dos-Santos AJ, Wakeham A, Ohashi PS, Cybulsky MI, Rudd CE, Penninger JM: Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Science 293;2260-2263, 2001 https://doi.org/10.1126/science.1063397
  54. Peterson EJ, Woods ML, Dmowski SA, Derimanov G, Jordan MS, Wu JN, Myung PS, Liu QH, Pribila JT, Freedman BD, Shimizu Y, Koretzky GA: Coupling of the TCR to integrin activation by Slap-130/Fyb. Science 293;2263-2265, 2001 https://doi.org/10.1126/science.1063486
  55. Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, Freund C, Kasirer-Friede A, Menasche G, Koretzky GA, Schraven B: The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Mol Cell Biol 26;7130-7144, 2006 https://doi.org/10.1128/MCB.00331-06
  56. Lafuente EM, van Puijenbroek AA, Krause M, Carman CV, Freeman GJ, Berezovskaya A, Constantine E, Springer TA, Gertler FB, Boussiotis VA: RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Dev Cell 7;585-595, 2004 https://doi.org/10.1016/j.devcel.2004.07.021
  57. Han J, Lim CJ, Watanabe N, Soriani A, Ratnikov B, Calderwood DA, Puzon-McLaughlin W, Lafuente EM, Boussiotis VA, Shattil SJ, Ginsberg MH: Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3. Curr Biol 16;1796-1806, 2006 https://doi.org/10.1016/j.cub.2006.08.035
  58. Sebzda E, Bracke M, Tugal T, Hogg N, Cantrell DA: Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling. Nat Immunol 3;251-258, 2002 https://doi.org/10.1038/ni765
  59. Katagiri K, Hattori M, Minato N, Kinashi T: Rap1 functions as a key regulator of T-cell and antigen-presenting cell interactions and modulates T-cell responses. Mol Cell Biol 22;1001-1015, 2002 https://doi.org/10.1128/MCB.22.4.1001-1015.2002
  60. Katagiri K, Hattori M, Minato N, Irie S, Takatsu K, Kinashi T: Rap1 is a potent activation signal for leukocyte function- associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase. Mol Cell Biol 20;1956-1969, 2000 https://doi.org/10.1128/MCB.20.6.1956-1969.2000
  61. Bos JL: Linking Rap to cell adhesion. Curr Opin Cell Biol 17;123-128, 2005 https://doi.org/10.1016/j.ceb.2005.02.009
  62. Menasche G, Kliche S, Chen EJ, Stradal TE, Schraven B, Koretzky G: RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation. Mol Cell Biol 27;4070-4081, 2007 https://doi.org/10.1128/MCB.02011-06
  63. Jordan MS, Sadler J, Austin JE, Finkelstein LD, Singer AL, Schwartzberg PL, Koretzky GA: Functional hierarchy of the N-terminal tyrosines of SLP-76. J Immunol 176;2430-2438, 2006 https://doi.org/10.4049/jimmunol.176.4.2430
  64. Jordan MS, Smith JE, Burns JC, Austin JE, Nichols KE, Aschenbrenner AC, Koretzky GA: Complementation in trans of altered thymocyte development in mice expressing mutant forms of the adaptor molecule SLP76. Immunity 28;359-369, 2008 https://doi.org/10.1016/j.immuni.2008.01.010
  65. Bezman NA, Lian L, Abrams CS, Brass LF, Kahn ML, Jordan MS, Koretzky GA: Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo. J Exp Med 205;1775-1788, 2008 https://doi.org/10.1084/jem.20080240

Cited by

  1. Phosphorylation Site Dynamics of Early T-cell Receptor Signaling vol.9, pp.8, 2009, https://doi.org/10.1371/journal.pone.0104240