SKAP55

Summary

Gene Symbol: SKAP55
Description: src kinase associated phosphoprotein 1
Alias: HEL-S-81p, SCAP1, SKAP55, src kinase-associated phosphoprotein 1, SKAP-55, epididymis secretory sperm binding protein Li 81p, pp55, src family-associated phosphoprotein 1, src kinase-associated phosphoprotein of 55 kDa
Species: human
Products:     SKAP55

Top Publications

  1. Raab M, Smith X, Matthess Y, Strebhardt K, Rudd C. SKAP1 protein PH domain determines RapL membrane localization and Rap1 protein complex formation for T cell receptor (TCR) activation of LFA-1. J Biol Chem. 2011;286:29663-70 pubmed publisher
    ..Further, N-terminal myr-tagged SKAP1 for membrane binding facilitated constitutive RapL membrane and Rap1 binding and effectively substituted for PI3K and TCR ligation in the activation of LFA-1 in T cells. ..
  2. Marie Cardine A, Hendricks Taylor L, Boerth N, Zhao H, Schraven B, Koretzky G. Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130. J Biol Chem. 1998;273:25789-95 pubmed
    ..We have recently cloned the 55-kDa protein that was termed Src kinase-associated phosphoprotein of 55 kDa (SKAP55)...
  3. Jo E, Wang H, Rudd C. An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R. J Exp Med. 2005;201:1733-9 pubmed
    ..Our findings therefore indicate that SKAP-55, unlike SKAP-55R, is specifically tailored as an essential component of the inside-out signaling events that couple the TCR to LFA-1 clustering and T cell-APC conjugation. ..
  4. Liu J, Kang H, Raab M, da Silva A, Kraeft S, Rudd C. FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells. Proc Natl Acad Sci U S A. 1998;95:8779-84 pubmed
    ..FYB as bait, we have identified eight clones, four of which correspond to the recently published lymphoid protein SKAP55, and two which correspond to a related protein with some 44% homology to SKAP55 (termed SKAP55-related protein, ..
  5. Wu L, Fu J, Shen S. SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription. Mol Cell Biol. 2002;22:2673-86 pubmed
    CD45 plays a critical role in T-cell receptor (TCR)-mediated signaling. In a yeast two-hybrid screen, SKAP55, the Src kinase-associated phosphoprotein of unknown function, was found as a substrate which associated with CD45 in vivo...
  6. Raab M, Wang H, Lu Y, Smith X, Wu Z, Strebhardt K, et al. T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes. Immunity. 2010;32:541-56 pubmed publisher
    ..Overall, our findings define a TCR "inside-out" pathway via N-SKAP1-C-RapL that regulates T cell adhesion, motility, and arrest times with DCs in LNs. ..
  7. Schraven B, Marie Cardine A, Koretzky G. Molecular analysis of the fyn-complex: cloning of SKAP55 and SLAP-130, two novel adaptor proteins which associate with fyn and may participate in the regulation of T cell receptor-mediated signaling. Immunol Lett. 1997;57:165-9 pubmed
  8. Marie Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer S, Schraven B. Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes. J Biol Chem. 1997;272:16077-80 pubmed
    ..Based on these properties the protein was termed SKAP55 (src kinase-associated phosphoprotein of 55 kDa)...
  9. Wang H, Moon E, Azouz A, Wu X, Smith A, Schneider H, et al. SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates. Nat Immunol. 2003;4:366-74 pubmed
    Src kinase-associated phosphoprotein of 55 kDa (SKAP-55; encoded by SCAP1) is a T cell adaptor protein of unknown function that contains a pleckstrin homology and an SH3 domain...

More Information

Publications40

  1. Huang Y, Norton D, Precht P, Martindale J, Burkhardt J, Wange R. Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells. J Biol Chem. 2005;280:23576-83 pubmed
    ADAP (adhesion and degranulation-promoting adaptor protein) and SKAP55 (Src kinase-associated phosphoprotein of 55 kDa) are T cell adaptors that mediate inside-out signaling from the T cell antigen receptor to integrins, giving rise to ..
  2. Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, et al. The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Mol Cell Biol. 2006;26:7130-44 pubmed
    ..Here, we show that a signaling module comprising the cytosolic adapter proteins ADAP and SKAP55 is involved in TCR-mediated inside-out signaling and, moreover, that the interaction between ADAP and SKAP55 is ..
  3. Kang H, Freund C, Duke Cohan J, Musacchio A, Wagner G, Rudd C. SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55. EMBO J. 2000;19:2889-99 pubmed
    ..In this study, we report SH3 domain binding to a novel proline-independent motif in immune cell adaptor SKAP55, which is comprised of two N-terminal lysine and arginine residues followed by two tyrosines (i.e. RKxxYxxY)...
  4. Duke Cohan J, Kang H, Liu H, Rudd C. Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein. J Biol Chem. 2006;281:13743-50 pubmed
    ..Our findings identify a RKXXY294 motif in SKAP-55 that mediates unique ADAP SH3c domain binding and is needed for LFA-1-mediated adhesion and cytokine production. ..
  5. Li C, Li W, Xiao J, Jiao S, Teng F, Xue S, et al. ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy. EMBO Mol Med. 2015;7:754-69 pubmed publisher
    ..In this study, we have identified that the ADAP-SKAP55 signaling module reduced CD8(+) CTL cytotoxicity and enhanced PD-1 expression in a Fyn-, Ca(2+)-, and NFATc1-..
  6. Raab M, Strebhardt K, Rudd C. Immune adaptor protein SKAP1 (SKAP-55) forms homodimers as mediated by the N-terminal region. BMC Res Notes. 2018;11:869 pubmed publisher
    ..SKAP1 dimer formation was not needed for its binding to RapL. These data indicate that the pathway linking SKAP1 to RapL is not dependent on the homo-dimerization of SKAP1. ..
  7. Yang Y, Wu L, Shu X, Lu Y, Shu X, Cai Q, et al. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk. Cancer Res. 2019;79:505-517 pubmed publisher
    ..SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression. ..
  8. Thaker Y, Schneider H, Rudd C. TCR and CD28 activate the transcription factor NF-κB in T-cells via distinct adaptor signaling complexes. Immunol Lett. 2015;163:113-9 pubmed publisher
    ..Overall, we provide evidence that CD28 and the TCR complex regulate NF-κB via different signaling modules of GRB-2/VAV1 and LAT/ADAP pathways respectively. ..
  9. Asai Y, Eslami A, van Ginkel C, Akhabir L, Wan M, Ellis G, et al. Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy. J Allergy Clin Immunol. 2018;141:991-1001 pubmed publisher
    ..Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression. ..
  10. Raab M, Lu Y, Köhler K, Smith X, Strebhardt K, Rudd C. LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation. Nat Commun. 2017;8:16001 pubmed publisher
    ..10 T cell binding to DCs and proliferation to OVA peptide. Overall, our findings outline a new model for LFA-1 in which the integrin can mediate both adhesion and de-adhesion events dependent on receptor cross-linking. ..
  11. Kasirer Friede A, Kang J, Kahner B, Ye F, Ginsberg M, Shattil S. ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding. Blood. 2014;123:3156-65 pubmed publisher
    ..Thus, ADAP uniquely promotes activation of and irreversible fibrinogen binding to platelet αIIbβ3 through interactions with talin and kindlin-3. ..
  12. Castorina G, Fox S, Tonelli C, Galbiati M, Conti L. A novel role for STOMATAL CARPENTER 1 in stomata patterning. BMC Plant Biol. 2016;16:172 pubmed publisher
    ..Previously, the DOF transcription factor STOMATAL CARPENTER 1 (SCAP1) was shown to be involved in GC function, by activating a set of GC-specific genes required for GC maturation and ..
  13. Dai X, Liu Z, Zhang S. Over-expression of EPS15 is a favorable prognostic factor in breast cancer. Mol Biosyst. 2015;11:2978-85 pubmed publisher
    ..In summary, over-expression of EPS15 is a potential favorable prognostic marker in breast cancer, which can be used clinically alone or together with other genes such as MSRA to avail therapeutic decision-making. ..
  14. Zhang Q, Dai H, Yatim K, Abou Daya K, Williams A, Oberbarnscheidt M, et al. CD8+ Effector T Cell Migration to Pancreatic Islet Grafts Is Dependent on Cognate Antigen Presentation by Donor Graft Cells. J Immunol. 2016;197:1471-6 pubmed publisher
    ..Therefore, effector T cell migration to transplanted islets is Ag driven, not chemokine driven, but SKAP1 does not play a critical role in this process. ..
  15. Goode E, Chenevix Trench G, Song H, Ramus S, Notaridou M, Lawrenson K, et al. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet. 2010;42:874-9 pubmed publisher
    ..Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development. ..
  16. Lehmann R, Meyer J, Schuemann M, Krause E, Freund C. A novel S3S-TAP-tag for the isolation of T-cell interaction partners of adhesion and degranulation promoting adaptor protein. Proteomics. 2009;9:5288-95 pubmed publisher
  17. Fang L, Seki A, Fang G. SKAP associates with kinetochores and promotes the metaphase-to-anaphase transition. Cell Cycle. 2009;8:2819-27 pubmed
  18. Huang C, Huang S, Pao J, Chang T, Lan Y, Lu T, et al. Genetic polymorphisms in androgen receptor-binding sites predict survival in prostate cancer patients receiving androgen-deprivation therapy. Ann Oncol. 2012;23:707-13 pubmed publisher
    ..001). Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression. ..
  19. Marie Cardine A, Kirchgessner H, Schraven B. Molecular alterations of the Fyn-complex occur as late events of human T cell activation. Eur J Immunol. 1999;29:1175-87 pubmed
    ..pp43, pp72, pp85, the protein tyrosine kinase Pyk2, as well as the two recently cloned adaptor proteins, SKAP55 and SLAP-130)...
  20. Ophir M, Liu B, Bunnell S. The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms. J Cell Biol. 2013;203:1021-41 pubmed publisher
    ..In addition to regulating integrin activation, we show that Src kinase-associated phosphoprotein of 55 kD (SKAP55) is required for microcluster persistence and movement, junctional stabilization, and integrin-independent ..
  21. Witte A, Meineke B, Sticht J, Philipsen L, Kuropka B, Müller A, et al. D120 and K152 within the PH Domain of T Cell Adapter SKAP55 Regulate Plasma Membrane Targeting of SKAP55 and LFA-1 Affinity Modulation in Human T Lymphocytes. Mol Cell Biol. 2017;37: pubmed publisher
    ..The Src kinase-associated phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling)...
  22. Kouroku Y, Soyama A, Fujita E, Urase K, Tsukahara T, Momoi T. RA70 is a src kinase-associated protein expressed ubiquitously. Biochem Biophys Res Commun. 1998;252:738-42 pubmed
    ..during neuronal differentiation of P19 EC, is highly homologous to human src kinase-associated phosphoprotein (SKAP55). Here we isolated human full-length RA70 cDNA...
  23. Smith X, Taylor A, Rudd C. T-cell immune adaptor SKAP1 regulates the induction of collagen-induced arthritis in mice. Immunol Lett. 2016;176:122-7 pubmed publisher
    ..SKAP1 therefore represents a novel connection to Th17 producing T-cells and is new potential target in the therapeutic intervention in autoimmune and inflammatory diseases. ..
  24. Cindric Vranesic A, Reiche J, Hoischen C, Wohlmann A, Bratsch J, Friedrich K, et al. Characterization of SKAP/kinastrin isoforms: the N-terminus defines tissue specificity and Pontin binding. Hum Mol Genet. 2016;25:2838-2852 pubmed
  25. Lim D, Lu Y, Rudd C. Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1. Immunol Lett. 2016;172:40-6 pubmed publisher
    ..SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation. ..
  26. Steffens M, Leu C, Ruppert A, Zara F, Striano P, Robbiano A, et al. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. Hum Mol Genet. 2012;21:5359-72 pubmed publisher
    ..1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes. ..
  27. KOSCO K, Cerignoli F, Williams S, Abraham R, Mustelin T. SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1. Mol Immunol. 2008;45:510-22 pubmed
    Src kinase-associated phosphoprotein of 55 kDa (SKAP55) is an adapter protein with an N-terminal region, a pleckstrin homology domain, a linker with tyrosine phosphorylation sites, and a C-terminal Src homology 3 domain...
  28. 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
  29. Clements J, Boerth N, Lee J, Koretzky G. Integration of T cell receptor-dependent signaling pathways by adapter proteins. Annu Rev Immunol. 1999;17:89-108 pubmed
  30. Xiong Y, Ye C, Yang N, Li M, Liu H. Ubc9 Binds to ADAP and Is Required for Rap1 Membrane Recruitment, Rac1 Activation, and Integrin-Mediated T Cell Adhesion. J Immunol. 2017;199:4142-4154 pubmed publisher
  31. Wu L, Yu Z, Shen S. SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation. J Biol Chem. 2002;277:40420-7 pubmed
    ..We observed that adapter protein SKAP55, the Src kinase-associated phosphoprotein, formed homodimers through its SH3 domain and SK region...