Lcp2

Summary

Gene Symbol: Lcp2
Description: lymphocyte cytosolic protein 2
Alias: AI323664, BB161688, SLP-76, SLP76, m1Khoe, twm, lymphocyte cytosolic protein 2, SH2 domain-containing leukocyte protein of 76 kDa, SLP-76 tyrosine phosphoprotein
Species: mouse
Products:     Lcp2

Top Publications

  1. Lenox L, Kambayashi T, Okumura M, Prieto C, Sauer K, Bunte R, et al. Mutation of tyrosine 145 of lymphocyte cytosolic protein 2 protects mice from anaphylaxis and arthritis. J Allergy Clin Immunol. 2009;124:1088-98 pubmed publisher
    b>Lymphocyte cytosolic protein 2, also known as Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76), is an essential adaptor molecule in myeloid cells, where it regulates FcepsilonRI-induced mast cell (MC) ..
  2. Judd B, Myung P, Obergfell A, Myers E, Cheng A, Watson S, et al. Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. J Exp Med. 2002;195:705-17 pubmed
  3. Myung P, Derimanov G, Jordan M, Punt J, Liu Q, Judd B, et al. Differential requirement for SLP-76 domains in T cell development and function. Immunity. 2001;15:1011-26 pubmed
  4. Judd B, Myung P, Leng L, Obergfell A, Pear W, Shattil S, et al. 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. 2000;97:12056-61 pubmed
    ..These studies establish that SLP-76 functions downstream of alpha IIb beta 3 and collagen receptors in platelets. Furthermore, expression of SLP-76 in hematopoietic cells, including platelets, plays a necessary role in hemostasis. ..
  5. Bezman N, Lian L, Abrams C, Brass L, Kahn M, Jordan M, et al. Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo. J Exp Med. 2008;205:1775-88 pubmed publisher
    Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP76), an adaptor that plays a critical role in platelet activation in vitro, contains three N-terminal tyrosine residues that are essential for its function...
  6. Pivniouk V, Martin T, Lu Kuo J, Katz H, Oettgen H, Geha R. SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells. J Clin Invest. 1999;103:1737-43 pubmed
    ..Bone marrow-derived mast cells (BMMCs) from SLP76(-/-) mice failed to release beta-hexosaminidase and to secrete IL-6 after FcepsilonRI cross-linking...
  7. Abtahian F, Bezman N, Clemens R, Sebzda E, Cheng L, Shattil S, et al. Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Mol Cell Biol. 2006;26:6936-49 pubmed
  8. Wang H, McCann F, Gordan J, Wu X, Raab M, Malik T, et al. ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. J Exp Med. 2004;200:1063-74 pubmed
    ..Our findings identify ADAP-SLP-76 binding as a signaling event that differentially regulates SMAC formation, and support a role for SMAC formation in T cell cytokine production. ..
  9. Krause M, Sechi A, Konradt M, Monner D, Gertler F, Wehland J. Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton. J Cell Biol. 2000;149:181-94 pubmed

More Information

Publications84

  1. 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
  2. Jordan M, Smith J, Burns J, Austin J, Nichols K, Aschenbrenner A, et al. Complementation in trans of altered thymocyte development in mice expressing mutant forms of the adaptor molecule SLP76. Immunity. 2008;28:359-69 pubmed publisher
    The adaptor protein SLP76 directs signaling downstream of the T cell receptor (TCR) and is essential for thymocyte development. SLP76 contains three N-terminal tyrosines that are critical for its function...
  3. Jordan M, Sadler J, Austin J, Finkelstein L, Singer A, Schwartzberg P, et al. Functional hierarchy of the N-terminal tyrosines of SLP-76. J Immunol. 2006;176:2430-8 pubmed
    ..These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo. ..
  4. Chiang Y, Sommers C, Jordan M, Gu H, Samelson L, Koretzky G, et al. Inactivation of c-Cbl reverses neonatal lethality and T cell developmental arrest of SLP-76-deficient mice. J Exp Med. 2004;200:25-34 pubmed
  5. 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
  6. Kettner A, Pivniouk V, Kumar L, Falet H, Lee J, Mulligan R, et al. Structural requirements of SLP-76 in signaling via the high-affinity immunoglobulin E receptor (Fc epsilon RI) in mast cells. Mol Cell Biol. 2003;23:2395-406 pubmed
    ..These results point to important differences in the function of SLP-76 between T cells and mast cells. ..
  7. Abtahian F, Guerriero A, Sebzda E, Lu M, Zhou R, Mocsai A, et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 2003;299:247-51 pubmed
    ..These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals...
  8. Clements J, Yang B, Ross Barta S, Eliason S, Hrstka R, Williamson R, et al. Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science. 1998;281:416-9 pubmed
    ..Thus, the SLP-76 adapter protein is required for normal thymocyte development and plays a crucial role in translating signals mediated by pre-T cell receptors into distal biochemical events. ..
  9. Clements J, Lee J, Gross B, Yang B, Olson J, Sandra A, et al. Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. J Clin Invest. 1999;103:19-25 pubmed
    ..These data provide one potential mechanism for the fetal hemorrhage observed in SLP-76-deficient mice and reveal that SLP-76 expression is required for optimal receptor-mediated signal transduction in platelets as well as T lymphocytes. ..
  10. Pivniouk V, Tsitsikov E, Swinton P, Rathbun G, Alt F, Geha R. Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76. Cell. 1998;94:229-38 pubmed
    ..V-D-J rearrangement of the TCRbeta locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes. ..
  11. Kumar L, Pivniouk V, de la Fuente M, Laouini D, Geha R. Differential role of SLP-76 domains in T cell development and function. Proc Natl Acad Sci U S A. 2002;99:884-9 pubmed
    ..These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions. ..
  12. Clemens R, Lenox L, Kambayashi T, Bezman N, Maltzman J, Nichols K, et al. Loss of SLP-76 expression within myeloid cells confers resistance to neutrophil-mediated tissue damage while maintaining effective bacterial killing. J Immunol. 2007;178:4606-14 pubmed
    ..aureus but reduction in LPS-induced tissue damage and vascular injury. ..
  13. 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. ..
  14. Yoder J, Pham C, Iizuka Y, Kanagawa O, Liu S, McGlade J, et al. Requirement for the SLP-76 adaptor GADS in T cell development. Science. 2001;291:1987-91 pubmed
    ..Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling. ..
  15. Yokosuka T, Sakata Sogawa K, Kobayashi W, Hiroshima M, Hashimoto Tane A, Tokunaga M, et al. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol. 2005;6:1253-62 pubmed
    ..Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling. ..
  16. Wu J, Jordan M, Silverman M, Peterson E, Koretzky G. 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. 2004;172:6768-74 pubmed
    ..Thus, failure to bind ADAP does not underlie the functional defects exhibited by SLP-76 SH2 domain mutant-expressing mast cells. ..
  17. May R, Okumura M, Hsu C, Bassiri H, Yang E, Rak G, et al. Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function. Blood. 2013;121:3135-46 pubmed publisher
    ..These results demonstrate that NK cells possess an unexpected bifurcation of proximal ITAM-mediated signaling, each involving SLP-76 and contributing to optimal NK-cell function. ..
  18. Maltzman J, Kovoor L, Clements J, Koretzky G. Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection. J Exp Med. 2005;202:893-900 pubmed
    ..These studies show for the first time that SLP-76 is required for signal transduction through the mature alphabeta TCR in primary cells of the T lineage. ..
  19. Corbo Rodgers E, Wiehagen K, Staub E, Maltzman J. Homeostatic division is not necessary for antigen-specific CD4+ memory T cell persistence. J Immunol. 2012;189:3378-85 pubmed
    ..These data suggest the independent maintenance of a population of Ag-specific CD4(+) memory T cells in the absence of SLP-76 and normal levels of homeostatic division. ..
  20. Hidano S, Kitamura D, Kumar L, Geha R, Goitsuka R. SLP-76 is required for high-affinity IgE receptor- and IL-3 receptor-mediated activation of basophils. Int Immunol. 2012;24:719-27 pubmed publisher
    ..Taken together, these findings indicate that SLP-76 is an essential signaling component for basophil activation downstream of both Fc?RI and the IL-3 receptor. ..
  21. Abudula A, Grabbe A, Brechmann M, Polaschegg C, Herrmann N, Goldbeck I, et al. SLP-65 signal transduction requires Src homology 2 domain-mediated membrane anchoring and a kinase-independent adaptor function of Syk. J Biol Chem. 2007;282:29059-66 pubmed
    ..Moreover, membrane anchoring of the SLP-65-assembled Ca(2+) initiation complex, which appears to be fundamentally different from that of closely related SLP-76, does not necessarily involve a B cell-specific component. ..
  22. Luckashenak N, Ryszkiewicz R, Ramsey K, Clements J. The Src homology 2 domain-containing leukocyte protein of 76-kDa adaptor links integrin ligation with p44/42 MAPK phosphorylation and podosome distribution in murine dendritic cells. J Immunol. 2006;177:5177-85 pubmed
  23. Sarratt K, Chen H, Zutter M, Santoro S, Hammer D, Kahn M. GPVI and alpha2beta1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood. 2005;106:1268-77 pubmed
    ..These studies establish platelet-collagen responses under physiologic flow as the consequence of a close partnership between 2 structurally distinct receptors and suggest that both receptors play significant hemostatic roles in vivo. ..
  24. 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. ..
  25. Reppschläger K, Gosselin J, Dangelmaier C, Thomas D, Carpino N, McKenzie S, et al. TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk. J Biol Chem. 2016;291:22427-22441 pubmed
    ..Putative biological functions of TULA-2-mediated dephosphorylation of Tyr(P)346 may include deactivation of receptor-activated Syk or suppression of Syk activation by suboptimal stimulation. ..
  26. Nichols K, Haines K, Myung P, Newbrough S, Myers E, Jumaa H, et al. 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 pubmed
    ..Taken together, these data suggest that neither SLP-76 nor SLP-65 is required during FcgammaR-dependent signaling and functional events in macrophages. ..
  27. 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. ..
  28. Corbo Rodgers E, Staub E, Zou T, Smith A, Kambayashi T, Maltzman J. Oral ivermectin as an unexpected initiator of CreT2-mediated deletion in T cells. Nat Immunol. 2012;13:197-8 pubmed publisher
  29. Boulaftali Y, Hess P, Getz T, Cholka A, Stolla M, Mackman N, et al. Platelet ITAM signaling is critical for vascular integrity in inflammation. J Clin Invest. 2013;123:908-16 pubmed publisher
  30. Bezman N, Baker R, Lenox L, Jordan M, Koretzky G. Cutting edge: rescue of pre-TCR but not mature TCR signaling in mice expressing membrane-targeted SLP-76. J Immunol. 2009;182:5183-7 pubmed publisher
    ..Thus, fixed localization of SLP-76 reveals differential requirements for the subcellular localization of signaling complexes downstream of the pre-TCR vs mature TCR. ..
  31. 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...
  32. Wiehagen K, Corbo E, Schmidt M, Shin H, Wherry E, Maltzman J. Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cells. Blood. 2010;116:5560-70 pubmed publisher
    ..Our data are consistent with a model in which tonic TCR signals are required at multiple stages of differentiation, but are dispensable for memory CD8 T-cell persistence. ..
  33. Zhong X, Maltzman J, Hainey E, Koretzky G. Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements. J Immunol. 2003;171:6621-9 pubmed
    ..The present study provides the first data to address the mechanisms controlling SLP-76 transcription by providing evidence for several key cis-regulatory elements in the promoter region. ..
  34. Carty S, Koretzky G, Jordan M. Interleukin-4 regulates eomesodermin in CD8+ T cell development and differentiation. PLoS ONE. 2014;9:e106659 pubmed publisher
  35. Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, et al. Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell. 2008;132:794-806 pubmed publisher
    ..Thus, this study reveals the importance of the osteoclastogenic signaling complex composed of tyrosine kinases, which may provide the molecular basis for a new therapeutic strategy...
  36. Leo L, Di Paola J, Judd B, Koretzky G, Lentz S. Role of the adapter protein SLP-76 in GPVI-dependent platelet procoagulant responses to collagen. Blood. 2002;100:2839-44 pubmed
    ..Thus, both GPVI-dependent and GPVI-independent pathways contribute to collagen-induced platelet procoagulant activity. ..
  37. 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
  38. Ramsey K, Luckashenak N, Koretzky G, Clements J. Impaired thymic selection in mice expressing altered levels of the SLP-76 adaptor protein. J Leukoc Biol. 2008;83:419-29 pubmed
  39. Bachmaier K, Krawczyk C, Kozieradzki I, Kong Y, Sasaki T, Oliveira dos Santos A, et al. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature. 2000;403:211-6 pubmed
    ..Cbl-b is thus a key regulator of activation thresholds in mature lymphocytes and immunological tolerance and autoimmunity. ..
  40. Freund J, May R, Yang E, Li H, McCullen M, Zhang B, et al. Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells. PLoS Biol. 2016;14:e1002526 pubmed publisher
  41. 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. ..
  42. Cao Y, Li H, Liu H, Zhang M, Hua Z, Ji H, et al. LKB1 regulates TCR-mediated PLC?1 activation and thymocyte positive selection. EMBO J. 2011;30:2083-93 pubmed publisher
    ..These observations indicated that LKB1 is a critical component involved in TCR signalling, and our studies provide novel insights into the mechanisms of LKB1-mediated thymocyte development. ..
  43. 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. ..
  44. 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. ..
  45. Hillen K, Gather R, Enders A, Pircher H, Aichele P, Fisch P, et al. T cell expansion is the limiting factor of virus control in mice with attenuated TCR signaling: implications for human immunodeficiency. J Immunol. 2015;194:2725-34 pubmed publisher
    ..Thus, under conditions of impaired TCR signaling, reduced T cell expansion was the limiting factor in antiviral immunity. These findings have implications for understanding antiviral immunity in patients with T cell deficiencies. ..
  46. Hidano S, Sasanuma H, Ohshima K, Seino K, Kumar L, Hayashi K, et al. Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production. Int Immunol. 2008;20:345-52 pubmed publisher
    ..Taken together, these results suggest that SLP-76 and MIST distinctly but interactively regulate NK cell cytotoxicity and IFN-gamma production. ..
  47. Luo H, Yu G, Tremblay J, Wu J. EphB6-null mutation results in compromised T cell function. J Clin Invest. 2004;114:1762-73 pubmed
    ..Further downstream, in the absence of EphB6, ZAP-70 activation, LAT phosphorylation, the association of PLCgamma1 with SLP-76, and p44/42 MAPK activation were diminished. Thus, we have shown that EphB6 is pivotal in T cell function. ..
  48. Pivniouk V, Geha R. The role of SLP-76 and LAT in lymphocyte development. Curr Opin Immunol. 2000;12:173-8 pubmed
    ..The data indicate that SLP-76 and LAT are each critical for the expansion and differentiation of double-negative thymocytes and that SLP-76 is essential for allelic exclusion at the TCRbeta locus. ..
  49. 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. ..
  50. Shen S, Lau J, Zhu M, Zou J, Fuller D, Li Q, et al. The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation. Blood. 2009;114:74-84 pubmed publisher
    ..Altogether, our data demonstrated that the SAM domain is indispensable for optimal SLP-76 signaling. ..
  51. Gordon S, Carty S, Kim J, Zou T, Smith Garvin J, ALONZO E, et al. Requirements for eomesodermin and promyelocytic leukemia zinc finger in the development of innate-like CD8+ T cells. J Immunol. 2011;186:4573-8 pubmed publisher
    ..Taken together, these data shed light on the cell-intrinsic and cell-extrinsic factors that drive CD8(+) ILL differentiation. ..
  52. Chang J, Ciocca M, Kinjyo I, Palanivel V, McClurkin C, Dejong C, et al. Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division. Immunity. 2011;34:492-504 pubmed publisher
    ..These results suggest a mechanism by which a cell may unequally localize cellular activities during division, thereby imparting disparity in the abundance of cell fate regulators in the daughter cells. ..
  53. 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
  54. Nishida K, Yamasaki S, Ito Y, Kabu K, Hattori K, Tezuka T, et al. Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane. J Cell Biol. 2005;170:115-26 pubmed
    ..Finally, we show that the Fyn/Gab2/RhoA (but not Lyn/SLP-76) signaling pathway plays a critical role in the calcium-independent microtubule-dependent pathway. ..
  55. Chen C, Bertozzi C, Zou Z, Yuan L, Lee J, Lu M, et al. Blood flow reprograms lymphatic vessels to blood vessels. J Clin Invest. 2012;122:2006-17 pubmed publisher
    ..Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in ..
  56. Zou T, Satake A, Corbo Rodgers E, Schmidt A, Farrar M, Maltzman J, et al. Cutting edge: IL-2 signals determine the degree of TCR signaling necessary to support regulatory T cell proliferation in vivo. J Immunol. 2012;189:28-32 pubmed publisher
    ..These findings also have therapeutic implications, as TCR signaling by Tregs may not be required when using IL-2 to increase Treg numbers for treatment of inflammatory disorders. ..
  57. Geng L, Rudd C. Signalling scaffolds and adaptors in T-cell immunity. Br J Haematol. 2002;116:19-27 pubmed
  58. Caton A, Kropf E, Simons D, Aitken M, Weissler K, Jordan M. Strength of TCR signal from self-peptide modulates autoreactive thymocyte deletion and Foxp3(+) Treg-cell formation. Eur J Immunol. 2014;44:785-93 pubmed publisher
  59. Bushar N, Corbo E, Schmidt M, Maltzman J, Farber D. Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis. Proc Natl Acad Sci U S A. 2010;107:827-31 pubmed publisher
  60. Block H, Herter J, Rossaint J, Stadtmann A, Kliche S, Lowell C, et al. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med. 2012;209:407-21 pubmed publisher
    ..By using genetically engineered mice and transduced Slp76(-/-) primary leukocytes, we demonstrate that ADAP as well as two N-terminal-located tyrosines and the SH2 domain ..
  61. Patzak I, Königsberger S, Suzuki A, Mak T, Kiefer F. HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion. Eur J Immunol. 2010;40:3220-5 pubmed publisher
    ..Altogether, these results describe a novel function for HPK1 in linking TCR signaling to cell adhesion regulation and provide a mechanistic explanation for the negative regulatory role of HPK1 in T-cell biology. ..
  62. Kambayashi T, Okumura M, Baker R, Hsu C, Baumgart T, Zhang W, et al. Independent and cooperative roles of adaptor molecules in proximal signaling during FcepsilonRI-mediated mast cell activation. Mol Cell Biol. 2010;30:4188-96 pubmed publisher
    ..We propose that while SLP-76 and LAT1 depend on each other for many of their functions, LAT2/SLP-76 interactions and SLP-76-independent LAT1 functions also mediate a positive signaling pathway downstream of FcepsilonRI in mast cells. ..
  63. Sebzda E, Hibbard C, Sweeney S, Abtahian F, Bezman N, Clemens G, et al. Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev Cell. 2006;11:349-61 pubmed
    ..These studies provide genetic evidence for hematopoietic contribution to vascular development and suggest that hematopoietic tissue can provide a source of vascular endothelial progenitor cells throughout life. ..
  64. Sosinowski T, Pandey A, Dixit V, Weiss A. Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling. J Exp Med. 2000;191:463-74 pubmed
    ..These results suggest that SLAP is a negative regulator of TCR signaling. ..
  65. 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. ..
  66. Jarvis G, Best D, Watson S. Glycoprotein VI/Fc receptor gamma chain-independent tyrosine phosphorylation and activation of murine platelets by collagen. Biochem J. 2004;383:581-8 pubmed
    ..These results illustrate a novel mechanism of platelet activation by collagen which is independent of the GPVI-FcRgamma chain complex, and is facilitated by binding of collagen to integrin alpha2beta1. ..
  67. Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, et al. Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol. 2014;15:384-392 pubmed publisher
    ..Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling. ..
  68. Siggs O, Miosge L, Daley S, Asquith K, Foster P, Liston A, et al. Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation. J Immunol. 2015;194:2587-95 pubmed publisher
    ..In this study we describe a splice variant of Lcp2 that reduced the amount of wild-type SLP-76 protein by ~90%, disrupting immunogenic and tolerogenic pathways to ..
  69. Peterson E, Clements J, Ballas Z, Koretzky G. NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein. Eur J Immunol. 1999;29:2223-32 pubmed
  70. Lampe K, Endale M, Cashman S, Fang H, Mattner J, Hildeman D, et al. Slp-76 is a critical determinant of NK-cell mediated recognition of missing-self targets. Eur J Immunol. 2015;45:2072-83 pubmed publisher
    ..Overall these studies establish Slp-76 as a critical determinant of NK-cell development and NK cell mediated elimination of missing-self target cells in mice. ..
  71. 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. ..
  72. Thaker Y, Recino A, Raab M, Jabeen A, Wallberg M, Fernandez N, et al. Activated Cdc42-associated kinase 1 (ACK1) binds the sterile ? motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines. J Biol Chem. 2017;292:6281-6290 pubmed publisher
    ..These findings identify ACK1 as a novel SLP-76-associated protein-tyrosine kinase that modulates early activation events in T cells. ..
  73. Smith Garvin J, Burns J, Gohil M, Zou T, Kim J, Maltzman J, et al. T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool. Blood. 2010;116:5548-59 pubmed publisher
    ..Furthermore, we show that TCR signals sufficient to promote CD8(+) T-cell differentiation are different from those required to elicit inflammatory cytokine production. ..
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    ..Finally, a yopH mutant survived better in the absence of neutrophils, indicating that neutrophil inactivation by YopH by targeting PRAM-1/SKAP-HOM and SLP-76/Vav/PLC?2 signaling hubs may be critical for Yersinia survival. ..
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    ..Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner. ..