SLP 76


Gene Symbol: SLP 76
Description: lymphocyte cytosolic protein 2
Alias: SLP-76, SLP76, lymphocyte cytosolic protein 2, 76 kDa tyrosine phosphoprotein, SH2 domain-containing leukocyte protein of 76 kDa, SLP-76 tyrosine phosphoprotein
Species: human
Products:     SLP 76

Top Publications

  1. Baker R, Hsu C, Lee D, Jordan M, Maltzman J, Hammer D, et al. The adapter protein SLP-76 mediates "outside-in" integrin signaling and function in T cells. Mol Cell Biol. 2009;29:5578-89 pubmed publisher
  2. Liu S, Fang N, Koretzky G, McGlade C. The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Curr Biol. 1999;9:67-75 pubmed
    ..Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways. ..
  3. Binstadt B, Billadeau D, Jevremovic D, Williams B, Fang N, Yi T, et al. SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors. J Biol Chem. 1998;273:27518-23 pubmed
  4. Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, et al. Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT. J Exp Med. 1999;189:1383-90 pubmed
    ..Our data suggest that Grf40 is an adaptor molecule involved in TCR-mediated signaling through a more efficient interaction than Grb2 with SLP-76 and LAT. ..
  5. 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. 2001;21:4208-18 pubmed
    ..Thus, TCR-induced activation of PLC-gamma1 entails the binding of PLC-gamma1 to both LAT and SLP-76, a finding that may underlie the requirement for both LAT and SLP-76 to mediate the optimal activation of PLC-gamma1. ..
  6. Sauer K, Liou J, Singh S, Yablonski D, Weiss A, Perlmutter R. 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 pubmed
  7. Singer A, Bunnell S, Obstfeld A, Jordan M, Wu J, Myung P, et al. Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J Biol Chem. 2004;279:15481-90 pubmed
    ..Furthermore, we provide direct evidence that SLP-76 localization and, in turn, function are dependent upon association with Gads. ..
  8. Shim E, Moon C, Lee G, Ha Y, Chae S, Lee J. 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 pubmed
    ..Collectively, these data suggest that SLP-76 may play a role in PI3K signaling pathways. ..
  9. Gerke C, Falkow S, Chien Y. The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. J Exp Med. 2005;201:361-71 pubmed
    ..This is the first example showing that a pathogen targets these adaptor proteins in the TCR signaling pathway, suggesting a novel mechanism by which pathogens may efficiently alter T cell-mediated immune responses...

More Information


  1. Vasiliver Shamis G, Cho M, Hioe C, Dustin M. Human immunodeficiency virus type 1 envelope gp120-induced partial T-cell receptor signaling creates an F-actin-depleted zone in the virological synapse. J Virol. 2009;83:11341-55 pubmed publisher
    ..We propose a model in which the F-actin-depleted zone formed within the target CD4 T cell enhances the reception of virions by releasing the physical barrier for HIV-1 entry and facilitating postentry events. ..
  2. Bubeck Wardenburg J, Pappu R, Bu J, Mayer B, Chernoff J, Straus D, et al. Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity. 1998;9:607-16 pubmed
    ..Hence, phosphorylation of linker proteins not only bridges the TCR-associated PTK, ZAP-70, with downstream effector proteins, but also provides a scaffold to integrate distinct signaling complexes to regulate T cell function. ..
  3. Motto D, Ross S, Wu J, Hendricks Taylor L, Koretzky G. Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production. J Exp Med. 1996;183:1937-43 pubmed
    ..Our data document the in vivo associations of SLP-76 with several proteins that potentially participate in T cell activation and implicate SLP-76 itself as an important molecule in TCR-mediated IL-2 production. ..
  4. Shim E, Jung S, Lee J. Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells. J Immunol. 2011;186:2926-35 pubmed publisher
    ..The results suggest that SLP-76 associates with p85 after T cell activation and that LAT recruits this complex to the membrane, leading to Akt activation. ..
  5. Grasis J, Guimond D, Cam N, Herman K, Magotti P, Lambris J, et al. In vivo significance of ITK-SLP-76 interaction in cytokine production. Mol Cell Biol. 2010;30:3596-609 pubmed publisher
    ..In view of the role of ITK as a regulator of Th2 cytokine expression, the data underscore the significance of ITK as a target for pharmacological intervention. ..
  6. Gross B, Lee J, Clements J, Turner M, Tybulewicz V, Findell P, et al. Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. J Biol Chem. 1999;274:5963-71 pubmed
    ..This work identifies SLP-76 as an important adapter molecule that is regulated by Syk and lies upstream of SLAP-130 and PLC-gamma2 in CRP-stimulated platelets. ..
  7. Nguyen K, Sylvain N, Bunnell S. T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity. 2008;28:810-21 pubmed publisher
    ..These data suggest a widely applicable model of costimulation, in which integrins promote sustained signaling by attenuating cytoskeletal movements that drive the centralization and inactivation of SLP-76 microclusters. ..
  8. Bogin Y, Ainey C, Beach D, Yablonski D. SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK. Proc Natl Acad Sci U S A. 2007;104:6638-43 pubmed
    ..We propose that SLP-76 is required for ITK activation; furthermore, an ongoing physical interaction between SLP-76 and ITK is required to maintain ITK in an active conformation. ..
  9. Beach D, Gonen R, Bogin Y, Reischl I, Yablonski D. Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1. J Biol Chem. 2007;282:2937-46 pubmed
    ..These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins. ..
  10. Bunnell S, Diehn M, Yaffe M, Findell P, Cantley L, Berg L. Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. J Biol Chem. 2000;275:2219-30 pubmed
    ..Together, these observations suggest that multivalent interactions recruit Itk to LAT-nucleated signaling complexes and facilitate the activation of LAT-associated phospholipase Cgamma1 by Itk. ..
  11. Raab M, da Silva A, Findell P, Rudd C. Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2. Immunity. 1997;6:155-64 pubmed
    ..10 induces IL-2 production without detectable Vav-SLP-76 binding. Therefore, despite effects of Vav-SLP-76 on IL-2 expression, Vav-SLP-76 binding per se is not essential for IL-2 production in all T cells. ..
  12. Bubeck Wardenburg J, Fu C, Jackman J, Flotow H, Wilkinson S, Williams D, et al. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. J Biol Chem. 1996;271:19641-4 pubmed
    ..As SLP-76 interacts with both Grb2 and phospholipase C-gamma1, these data indicate that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways. ..
  13. Pauker M, Hassan N, Noy E, Reicher B, Barda Saad M. Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET. Sci Signal. 2012;5:rs3 pubmed publisher
    ..We suggest that these findings revise the accepted model of the formation of a complex of SLP-76, Nck, and Vav1 and demonstrate the use of 3FRET as a tool to study signal transduction in live cells. ..
  14. Kuhne M, Lin J, Yablonski D, Mollenauer M, Ehrlich L, Huppa J, et al. Linker for activation of T cells, zeta-associated protein-70, and Src homology 2 domain-containing leukocyte protein-76 are required for TCR-induced microtubule-organizing center polarization. J Immunol. 2003;171:860-6 pubmed
    ..Moreover, our studies revealed that a calcium-dependent event not requiring calcineurin or calcium/calmodulin-dependent kinase is required for TCR-induced polarization of the MTOC. ..
  15. Abraham L, Bankhead P, Pan X, Engel U, Fackler O. HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation. J Immunol. 2012;189:1898-910 pubmed publisher
    ..Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs. ..
  16. Berry D, Nash P, Liu S, Pawson T, McGlade C. 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 pubmed
    ..These results provide a molecular explanation for the specific role of Gads in T cell receptor signaling, and identify a discrete subclass of SH3 domains whose binding is dependent on a core R-X-X-K motif. ..
  17. Sela M, Bogin Y, Beach D, Oellerich T, Lehne J, Smith Garvin J, et al. Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. EMBO J. 2011;30:3160-72 pubmed publisher
  18. Jackman J, Motto D, Sun Q, Tanemoto M, Turck C, Peltz G, et al. Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. J Biol Chem. 1995;270:7029-32 pubmed
    ..These results demonstrate that this novel protein, which we term SLP-76 (SH2 domain-containing Leukocyte Protein of 76 kDa), is likely to play an important role in TCR-mediated intracellular signal transduction. ..
  19. Liu H, Purbhoo M, Davis D, Rudd C. SH2 domain containing leukocyte phosphoprotein of 76-kDa (SLP-76) feedback regulation of ZAP-70 microclustering. Proc Natl Acad Sci U S A. 2010;107:10166-71 pubmed publisher
    ..Our findings reconfigure the TCR signaling pathway by showing SLP-76 back-regulation of ZAP-70, an event that could ensure that signaling components are in balance for optimal T cell activation. ..
  20. Rivero Lezcano O, Marcilla A, Sameshima J, Robbins K. Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. Mol Cell Biol. 1995;15:5725-31 pubmed
    ..The main p47nck region implicated in the association with p66WASP was found to be the carboxy-terminal SH3 domain. ..
  21. Fu C, Turck C, Kurosaki T, Chan A. BLNK: a central linker protein in B cell activation. Immunity. 1998;9:93-103 pubmed
    ..Hence, BLNK represents a central linker protein that bridges the B cell receptor-associated kinases with a multitude of signaling pathways and may regulate the biologic outcomes of B cell function and development. ..
  22. Fang N, Koretzky G. SLP-76 and Vav function in separate, but overlapping pathways to augment interleukin-2 promoter activity. J Biol Chem. 1999;274:16206-12 pubmed
    ..These findings suggest that the synergy between SLP-76 and Vav in regulating IL-2 gene expression reflects the cooperation between different signaling pathways. ..
  23. Wu J, Motto D, Koretzky G, Weiss A. Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity. 1996;4:593-602 pubmed
    ..These results suggest that a signaling complex containing Vav and SLP-76 plays an important role in lymphocyte activation. ..
  24. Schneider H, Guerette B, Guntermann C, Rudd C. Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells. J Biol Chem. 2000;275:3835-40 pubmed
    ..These observations support a model where the TcR can utilize Rlk (as well as ZAP-70) in the phosphorylation of key sites in SLP-76 leading to the up-regulation of Th1 preferred cytokine IL-2. ..
  25. Brdicka T, Pavlistová D, Leo A, Bruyns E, Korinek V, Angelisova P, 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;191:1591-604 pubmed
    ..These findings collectively suggest that in the absence of external stimuli, the PAG-Csk complex transmits negative regulatory signals and thus may help to keep resting T cells in a quiescent state. ..
  26. Barda Saad M, Braiman A, Titerence R, Bunnell S, Barr V, Samelson L. Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nat Immunol. 2005;6:80-9 pubmed
    ..Thus, actin polymerization regulated by the TCR begins at the TCR. Molecules recruited to the TCR regulate actin polymerization and this process drives plasma membrane movement and cellular spreading. ..
  27. Ishiai M, Kurosaki M, Inabe K, Chan A, Sugamura K, Kurosaki T. Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane. J Exp Med. 2000;192:847-56 pubmed
    ..Hence, these data suggest a functional overlap between BLNK and SLP-76, while emphasizing the difference in requirement for additional adaptor molecules in their targeting to GEMs. ..
  28. Musci M, Hendricks Taylor L, Motto D, Paskind M, Kamens J, Turck C, et al. 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 pubmed
    ..These data suggest that SLP-76 recruits a negative regulator, SLAP-130, as well as positive regulators of signal transduction in T cells. ..
  29. da Silva A, Li Z, de Vera C, Canto E, Findell P, Rudd C. 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. 1997;94:7493-8 pubmed
    ..10, in response to TcRzeta/CD3 ligation. FYB is therefore a novel hematopoietic protein that acts as a component of the FYN and SLP-76 signaling cascades in T cells. ..
  30. Su Y, Zhang Y, Schweikert J, Koretzky G, Reth M, Wienands J. Interaction of SLP adaptors with the SH2 domain of Tec family kinases. Eur J Immunol. 1999;29:3702-11 pubmed
    ..Our findings suggest that Btk/Itk and phospholipase C-gamma both bind via their SH2 domain to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C-gamma. ..
  31. Veale M, Raab M, Li Z, da Silva A, Kraeft S, Weremowicz S, et al. Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production. J Biol Chem. 1999;274:28427-35 pubmed
    ..1. FYB-130 therefore represents a novel variant of FYB protein that can up-regulate T-cell receptor-driven interleukin 2 production in mature T-cells. ..
  32. Barda Saad M, Shirasu N, Pauker M, Hassan N, Perl O, Balbo A, et al. Cooperative interactions at the SLP-76 complex are critical for actin polymerization. EMBO J. 2010;29:2315-28 pubmed publisher
    ..Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation. ..
  33. Wunderlich L, Farago A, Downward J, Buday L. Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes. Eur J Immunol. 1999;29:1068-75 pubmed
    ..These results suggest that the Nck adaptor protein interacts with key signaling molecules and may play an important role in activation of T lymphocytes. ..
  34. Zhang W, Sloan Lancaster J, Kitchen J, Trible R, Samelson L. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 1998;92:83-92 pubmed
    ..Its function is demonstrated by inhibition of T cell activation following overexpression of a mutant form lacking critical tyrosine residues. Therefore, we propose to name the molecule LAT-linker for activation of T cells. ..
  35. Moltu K, Henjum K, Oberprieler N, Bjørnbeth B, Tasken K. Proximal signaling responses in peripheral T cells from colorectal cancer patients are affected by high concentrations of circulating prostaglandin E2. Hum Immunol. 2017;78:129-137 pubmed publisher
    ..T cell signaling responses downstream of the T cell receptor (assessed by reduced phosphorylation of CD3? and SLP76), and after triggering the IL-2 receptor (assessed by reduced phosphorylation of STAT5) when compared to T cells ..
  36. Bell Temin H, Culver Cochran A, Chaput D, Carlson C, Kuehl M, Burkhardt B, et al. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics. Mol Cell Proteomics. 2015;14:3173-84 pubmed publisher
    ..Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells. ..
  37. Hem C, Sundvold Gjerstad V, Granum S, Koll L, Abrahamsen G, Buday L, et al. T cell specific adaptor protein (TSAd) promotes interaction of Nck with Lck and SLP-76 in T cells. Cell Commun Signal. 2015;13:31 pubmed publisher
    ..Expression of TSAd increases both Nck-Lck and Nck-SLP-76 interaction in T cells. Recruitment of Lck and SLP-76 to Nck by TSAd could be one mechanism by which TSAd promotes actin polymerization in activated T cells. ..
  38. Hussain A, Mohammad D, Gustafsson M, Uslu M, Hamasy A, Nore B, et al. Signaling of the ITK (interleukin 2-inducible T cell kinase)-SYK (spleen tyrosine kinase) fusion kinase is dependent on adapter SLP-76 and on the adapter function of the kinases SYK and ZAP70. J Biol Chem. 2013;288:7338-50 pubmed publisher
    ..Altogether, our data suggest that ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor. ..
  39. Navas V, Cuche C, Alcover A, Di Bartolo V. Serine Phosphorylation of SLP76 Is Dispensable for T Cell Development but Modulates Helper T Cell Function. PLoS ONE. 2017;12:e0170396 pubmed publisher
    The adapter protein SLP76 is a key orchestrator of T cell receptor (TCR) signal transduction...
  40. Hashimoto Tane A, Sakuma M, Ike H, Yokosuka T, Kimura Y, Ohara O, et al. Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation. J Exp Med. 2016;213:1609-25 pubmed publisher
    ..transient but especially sustained upon weak TCR stimulation to recruit linker for activation of T cells (LAT) and SLP76. Perturbation of the micro-adhesion ring induced impairment of TCR-MC development and resulted in impaired ..
  41. Dezorella N, Katz B, Shapiro M, Polliack A, Perry C, Herishanu Y. SLP76 integrates into the B-cell receptor signaling cascade in chronic lymphocytic leukemia cells and is associated with an aggressive disease course. Haematologica. 2016;101:1553-1562 pubmed
    ..Here we show, for the first time, that SLP76, a key scaffold protein in T-cell receptor signaling, is ectopically expressed in chronic lymphocytic leukemia ..
  42. Lewitzky M, Kardinal C, Gehring N, Schmidt E, Konkol B, Eulitz M, et al. The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif. Oncogene. 2001;20:1052-62 pubmed
  43. Kremer K, Humphreys T, Kumar A, Qian N, Hedin K. Distinct role of ZAP-70 and Src homology 2 domain-containing leukocyte protein of 76 kDa in the prolonged activation of extracellular signal-regulated protein kinase by the stromal cell-derived factor-1 alpha/CXCL12 chemokine. J Immunol. 2003;171:360-7 pubmed
    ..Together, our results describe the distinct mechanism by which SDF-1alpha stimulates prolonged ERK activation in T cells and indicate that this pathway is specific for cells expressing both ZAP-70 and SLP-76. ..
  44. Kumar L, Feske S, Rao A, Geha R. A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function. Proc Natl Acad Sci U S A. 2005;102:19063-8 pubmed
    ..These results indicate that the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function. ..
  45. Charvet C, Canonigo A, Billadeau D, Altman A. Membrane localization and function of Vav3 in T cells depend on its association with the adapter SLP-76. J Biol Chem. 2005;280:15289-99 pubmed
    ..Altogether, our data show that TCR-induced association of Vav3 with SLP-76 is required for its membrane/IS localization and function. ..
  46. Sonnenberg G, Mangan P, Bezman N, Sekiguchi D, Luning Prak E, Erikson J, et al. Mislocalization of SLP-76 leads to aberrant inflammatory cytokine and autoantibody production. Blood. 2010;115:2186-95 pubmed publisher
    ..Thus, the abnormal effector T-cell phenotype still occurs in the presence of preserved central and peripheral tolerance, suggesting that diminished T-cell receptor signaling can promote skewed T-cell responses. ..
  47. Dennehy K, Elias F, Na S, Fischer K, Hunig T, Luhder F. Mitogenic CD28 signals require the exchange factor Vav1 to enhance TCR signaling at the SLP-76-Vav-Itk signalosome. J Immunol. 2007;178:1363-71 pubmed
    ..Our results indicate that CD28 signals feed into the TCR signaling pathway at the level of the SLP-76 signalosome. ..
  48. Gonen R, Beach D, Ainey C, Yablonski D. T cell receptor-induced activation of phospholipase C-gamma1 depends on a sequence-independent function of the P-I region of SLP-76. J Biol Chem. 2005;280:8364-70 pubmed
  49. Lee D, Kim J, Baker R, Koretzky G, Hammer D. SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow. Eur J Immunol. 2012;42:2736-43 pubmed publisher
    ..We further demonstrate the N-terminal phosphotyrosines of SLP-76 play a critical role in T-cell adhesion under flow. These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking. ..
  50. Abraham L, Fackler O. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun Signal. 2012;10:39 pubmed publisher
    ..We also discuss the implications of these alterations in the context of HIV-1 infection and in light of current concepts of TCR signal transduction. ..
  51. Danzer C, Koller A, Baier J, Arnold H, Giessler C, Opoka R, et al. A mutation within the SH2 domain of slp-76 regulates the tissue distribution and cytokine production of iNKT cells in mice. Eur J Immunol. 2016;46:2121-36 pubmed publisher
    ..Thus, slp-76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP-dependent and -independent mechanisms. ..
  52. Cao L, Ding Y, Hung N, Yu K, Ritz A, Raphael B, et al. Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells. PLoS ONE. 2012;7:e46725 pubmed publisher
    ..Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway. ..
  53. Mizuno K, Tagawa Y, Watanabe N, Ogimoto M, Yakura H. SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation. Eur J Immunol. 2005;35:644-54 pubmed
    ..Given that SHP-1 binds to CD22 upon BCR ligation, our findings suggest that dephosphorylation of SLP-76 recruited to CD22 by SHP-1 inhibits BCR-induced JNK activation, dictating apoptosis. ..
  54. Wang X, Li J, Chiu L, Lan J, Chen D, Boomer J, et al. Attenuation of T cell receptor signaling by serine phosphorylation-mediated lysine 30 ubiquitination of SLP-76 protein. J Biol Chem. 2012;287:34091-100 pubmed publisher
    ..These results reveal a novel regulation mechanism of SLP-76 by ubiquitination and proteasomal degradation of activated SLP-76, which is mediated by Ser-376 phosphorylation, leading to down-regulation of TCR signaling. ..
  55. Shah N, Wang Q, Yan Q, Karandur D, Kadlecek T, Fallahee I, et al. An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor. elife. 2016;5: pubmed publisher
    ..The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response of T cells to foreign antigens. ..
  56. Coussens N, Hayashi R, Brown P, Balagopalan L, Balbo A, Akpan I, et al. Multipoint binding of the SLP-76 SH2 domain to ADAP is critical for oligomerization of SLP-76 signaling complexes in stimulated T cells. Mol Cell Biol. 2013;33:4140-51 pubmed publisher
    ..These data support a model whereby multipoint binding of SLP-76 to ADAP facilitates the assembly of SLP-76 microclusters. This model has implications for the regulation of SLP-76 and LAT microclusters and, as a result, T cell signaling. ..
  57. Lindholm C, Henriksson M, Hallberg B, Welsh M. Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells. Eur J Biochem. 2002;269:3279-88 pubmed
    ..Our results indicate that upon TCR stimulation, Shb is targeted to these lipid rafts where Shb aids in recruiting the SLP-76-Gads-Vav complex to the T cell receptor zeta-chain and ZAP70. ..
  58. Liu H, Schneider H, Recino A, Richardson C, Goldberg M, Rudd C. The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells. Mol Cell. 2015;59:840-9 pubmed publisher
    ..Overall, we have identified SLP-76 as a direct regulator of nuclear pore function in T cells. ..
  59. Ellis J, Ashman C, Burden M, Kilpatrick K, Morse M, Hamblin P. GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28. J Immunol. 2000;164:5805-14 pubmed
    ..These findings suggest that GRID functions as an adapter protein in the CD28-mediated costimulatory pathway in T cells. ..
  60. Jung S, Yoo E, Yu M, Song H, Kang H, Cho J, et al. ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling and Integrin-Mediated Adhesion. J Immunol. 2016;197:942-52 pubmed publisher
  61. Wu G, Corbo E, Schmidt M, Smith Garvin J, Riese M, Jordan M, et al. Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses. Eur J Immunol. 2011;41:2064-73 pubmed publisher
  62. Bertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi M, et al. Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells. Cell Growth Differ. 2001;12:193-200 pubmed
  63. Xie J, Liang J, Diao L, Altman A, Li Y. TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter. J Immunol. 2013;190:4027-36 pubmed publisher
  64. Barr V, Sherman E, Yi J, Akpan I, Rouquette Jazdanian A, Samelson L. Development of nanoscale structure in LAT-based signaling complexes. J Cell Sci. 2016;129:4548-4562 pubmed
    ..These results demonstrate that the nanoscale organization of LAT-based signaling complexes is dynamic and indicates that different kinds of LAT-based complexes appear at different times during T cell activation. ..
  65. Liu H, Thaker Y, Stagg L, Schneider H, Ladbury J, Rudd C. SLP-76 sterile α motif (SAM) and individual H5 α helix mediate oligomer formation for microclusters and T-cell activation. J Biol Chem. 2013;288:29539-49 pubmed publisher
    ..Our data identified for the first time a role for the SAM domain in mediating SLP-76 self-association for T-cell function. ..
  66. Geng L, Raab M, Rudd C. Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651. J Immunol. 1999;163:5753-7 pubmed
    ..These observations define a pathway by which SLP-76 interacts with downstream components in the up-regulation of T cell cytokine production. ..
  67. Shen M, Yen A. c-Cbl tyrosine kinase-binding domain mutant G306E abolishes the interaction of c-Cbl with CD38 and fails to promote retinoic acid-induced cell differentiation and G0 arrest. J Biol Chem. 2009;284:25664-77 pubmed publisher
    ..The results demonstrate the importance of the Gly306 residue in the ability of c-Cbl to propel RA-induced differentiation. ..
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    ..Moreover, they underscore the importance of ezrin and Dlg1 in the regulation of NF-AT activation through p38. ..