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Revision as of 14:37, 6 September 2012


Src kinase associated phosphoprotein 1
File:PBB Protein SKAP1 image.jpg
PDB rendering based on 1u5d.
Available structures
PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB
Identifiers
Symbols SKAP1 ; SCAP1; SKAP55
External IDs Template:OMIM5 Template:MGI HomoloGene: 2764
RNA expression pattern
File:PBB GE SKAP1 205790 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Src kinase associated phosphoprotein 1, also known as SKAP1, is a human gene.[1]

This gene encodes a T cell adaptor protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adaptor protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins.[1]

The demonstration that SKAP1 regulates LFA-1 adhesion was made by retroviral infection [2] and by the SKAP1 deficient mouse [3]. Additional work has implicated SKAP1 in binding to the exchange factor RasGRP1 and in regulating ERK activation in T-cells [4][5].

References

  1. ↑ 1.0 1.1 "Entrez Gene: SKAP1 src kinase associated phosphoprotein 1".
  2. ↑ Wang H, Moon EY, Azouz A; et al. (2003). "SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates". Nat. Immunol. 4 (4): 366–74. doi:10.1038/ni913. PMID 12652296.
  3. ↑ Wang H, Liu H, Lu Y, Lovatt M, Wei, B, Rudd CE Functional defects of SKAP-55 deficient T-cells identify a regulatory role for the adaptor in LFA-1 adhesion, Mol. Cell. Biol. 2007 27, 6863-75.
  4. ↑ *Kosco KA, Cerignoli F, Williams S; et al. (2008). "SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1". Mol. Immunol. 45 (2): 510–22. doi:10.1016/j.molimm.2007.05.024. PMID 17658605.
  5. ↑ Schneider H., Wang H., Raab M., Valk E., Smith X. , Lovatt M., Wu Z., Strebhardt K, Rudd, CE. Adaptor SKAP55 binds RasGRP1 and negatively regulates p21ras and the ERK pathway in T-cells. (2008) PLoS ONE. 3, 1718.

Further reading

  • Schraven B, Marie-Cardine A, Koretzky G (1997). "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. 57 (1–3): 165–9. PMID 9232446.
  • Clements JL, Boerth NJ, Lee JR, Koretzky GA (1999). "Integration of T cell receptor-dependent signaling pathways by adapter proteins". Annu. Rev. Immunol. 17: 89–108. doi:10.1146/annurev.immunol.17.1.89. PMID 10358754.
  • Marie-Cardine A, Bruyns E, Eckerskorn C; et al. (1997). "Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes". J. Biol. Chem. 272 (26): 16077–80. PMID 9195899.
  • Liu J, Kang H, Raab M; et al. (1998). "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. 95 (15): 8779–84. PMID 9671755.
  • Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ; et al. (1998). "Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130". J. Biol. Chem. 273 (40): 25789–95. PMID 9748251.
  • Kouroku Y, Soyama A, Fujita E; et al. (1999). "RA70 is a src kinase-associated protein expressed ubiquitously". Biochem. Biophys. Res. Commun. 252 (3): 738–42. doi:10.1006/bbrc.1998.9637. PMID 9837776.
  • Kang H, Freund C, Duke-Cohan JS; et al. (2000). "SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55". EMBO J. 19 (12): 2889–99. doi:10.1093/emboj/19.12.2889. PMID 10856234.
  • Wu L, Fu J, Shen SH (2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Mol. Cell. Biol. 22 (8): 2673–86. PMID 11909961.
  • Wu L, Yu Z, Shen SH (2002). "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". J. Biol. Chem. 277 (43): 40420–7. doi:10.1074/jbc.M206023200. PMID 12171928.
  • Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
  • Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.
  • Huang Y, Norton DD, Precht P; et al. (2005). "Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells". J. Biol. Chem. 280 (25): 23576–83. doi:10.1074/jbc.M413201200. PMID 15849195.
  • Jo EK, Wang H, Rudd CE (2005). "An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R". J. Exp. Med. 201 (11): 1733–9. doi:10.1084/jem.20042577. PMID 15939789.
  • Duke-Cohan JS, Kang H, Liu H, Rudd CE (2006). "Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein". J. Biol. Chem. 281 (19): 13743–50. doi:10.1074/jbc.M508774200. PMID 16461356.
  • Kliche S, Breitling D, Togni M; et al. (2006). "The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1". Mol. Cell. Biol. 26 (19): 7130–44. doi:10.1128/MCB.00331-06. PMID 16980616.

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