Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

SLP-76

  • Jong Ran Lee
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_474

Synonyms

Historical Background

SLP-76 was first identified as a substrate of the protein tyrosine kinases that are activated by T-cell antigen receptors (TCRs) (Jackman et al. 1995). SLP-76, which functions as a signal transducer downstream of TCRs, is an adaptor protein that has three modular domains: an amino (N)-terminal acidic domain with three tyrosine (Y) phosphorylation motifs, a central proline-rich region, and a carboxy (C)-terminal SH2 domain (Fig. 1). Two other proteins, B-cell linker protein (BLNK/BASH/BCA/SLP-65) and cytokine-dependent hematopoietic cell linker (CLNK/MIST), constitute a family of SLP-76 adaptors, each expressed exclusively in hematopoietic cells. The three family members have only a moderate degree of sequence homology, but share a characteristic domain structure (Fig. 1). These SLP-76 family members are critical for nucleation of large signaling...
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References

  1. Abtahian F, Guerriero A, Sebzda E, MM L, 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. 2003;299:247–51.PubMedPubMedCentralGoogle Scholar
  2. Berry DM, Nash P, Liu SK, Pawson T, McGlade CJ. A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling. Curr Biol. 2002;12:1336–41.PubMedPubMedCentralGoogle Scholar
  3. Clements JL, Yang B, Ross-Barta SE, Eliason SL, Hrstka RF, Williamson RA, Koretzky GA. Requirement for the leukocyte-specific adaptor protein SLP-76 for normal T cell development. Science. 1998;281:416–9.PubMedPubMedCentralGoogle Scholar
  4. Gonen R, Beach D, Ainey C, Yablonski D. T cell receptor-induced activation of phospholipase C-gamma 1 depends on a sequence-independent function of the P-I region of SLP-76. J Biol Chem. 2005;280:8364–70.PubMedPubMedCentralGoogle Scholar
  5. Hassan NJ, Simmonds SJ, Clarkson NG, Hanrahan S, Puklavec MJ, Bomb M, Barclay AN, Brown MH. CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP76. Mol Cell Biol. 2006;26:6727–38.PubMedPubMedCentralGoogle Scholar
  6. Horn J, Wang X, Reichardt P, Stradal TE, Warnecke N, Simeoni L, Gunzer M, Yablonski D, Schraven B, Kliche S. Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa is mandatory for TCR-mediated inside-out signaling, but dispensable for CXCR4-mediated LFA-1 activation, adhesion, and migration of T cells. J Immunol. 2009;183:5756–67.PubMedPubMedCentralGoogle Scholar
  7. 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. 1995;270:7029–32.PubMedPubMedCentralGoogle Scholar
  8. 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. 2002;195:705–17.PubMedPubMedCentralGoogle Scholar
  9. Jung SH, Jeong JH, Seul HJ, Lee JR. Competition between SLP76 and LAT for PLC?1 binding in resting T cells. Eur J Immunol. 2010;40:2330–9.PubMedPubMedCentralGoogle Scholar
  10. 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 Biol Chem. 1997;272:11674–7.PubMedPubMedCentralGoogle Scholar
  11. Newbrough SA, Mocsai A, Clemens RA, JN W, Silverman MA, Singer AL, Lowell CA, Koretzky GA. SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils. Immunity. 2003;19:761–9.PubMedPubMedCentralGoogle Scholar
  12. Nichols KE, Haines K, Myung PS, Newbrough S, Myers E, Jumaa H, Shedlock DJ, Shen H, Koretzky GA. Macrophage activation and Fcgamma receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors. J Leukoc Biol. 2004;75:541–52.PubMedPubMedCentralGoogle Scholar
  13. Peterson EJ, Clements JL, Ballas ZK, Koretzky GA. NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein. Eur J Immunol. 1999;29:2223–32.PubMedPubMedCentralGoogle Scholar
  14. 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. 1999;103:1737–43.PubMedPubMedCentralGoogle Scholar
  15. Sanzenbacher R, Kabelitz D, Janssen O. SLP-76 binding to p56lck: a role for SLP-76 in CD4-induced desensitization of the TCR/CD3 signaling complex. J Immunol. 1999;163:3143–52.PubMedPubMedCentralGoogle Scholar
  16. 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. 2001;276:45207–16.PubMedPubMedCentralGoogle Scholar
  17. Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR. Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase. FEBS Lett. 2004;575:35–40.PubMedPubMedCentralGoogle Scholar
  18. Shui JW, Boomer JS, Han J, Xu J, Dement GA, Zhou G, Tan TH. Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell-mediated immune responses. Nat Immunol. 2007;8:84–91.PubMedPubMedCentralGoogle Scholar
  19. 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. 1999;29(11):3702.PubMedPubMedCentralGoogle Scholar
  20. Wu J, Motto DG, Koretzky GA, Weiss A. Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity. 1996;4:593–602.PubMedPubMedCentralGoogle Scholar
  21. Wunderlich L, Farago A, Downward J, Buday L. Association of Nck with tyrosine-phosphorylated SLP76 in activated T lymphocytes. Eur J Immunol. 1999;29:1068–75.PubMedPubMedCentralGoogle Scholar
  22. Yablonski D, Kuhne MR, Kadlecek T, Weiss A. Uncoupling of nonreceptor tyrosine kinases from PLC-?1 in an SLP-76-deficient T cell. Science. 1998;281:413–6.PubMedPubMedCentralGoogle Scholar
  23. Yablonski D, Kadlecek T, Weiss A. Identification of a phospholipase C-?1 (PLC-?1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-?1 and NFAT. Mol Cell Biol. 2001;21:4208–18.PubMedPubMedCentralGoogle Scholar
  24. Zeng R, Cannon JL, Abraham RT, Way M, Billadeau DD, Bubeck-Wardenberg J, Burkhardt JK. SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. J Immunol. 2003;171:1360–8.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Life Science, College of Natural SciencesEwha Womans UniversitySeoulKorea