SKAP1

Src kinase associated phosphoprotein 1

PDB rendering based on 1u5d.
Identifiers
Symbols SKAP1; SCAP1; SKAP55
External IDs OMIM: 604969 MGI: 1925723 HomoloGene: 2764 GeneCards: SKAP1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 8631 78473
Ensembl ENSG00000141293 ENSMUSG00000057058
UniProt Q86WV1 Q3UUV5
RefSeq (mRNA) NM_001075099.1 NM_001033186
RefSeq (protein) NP_001068567.1 NP_001028358
Location (UCSC) Chr 17:
46.21 – 46.51 Mb		 Chr 11:
96.33 – 96.62 Mb
PubMed search [1] [2]

Src kinase-associated phosphoprotein 1 is an adapter protein that in humans is encoded by the SKAP1 gene.[1][2]

This gene encodes a T cell adapter 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 adapter protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins.[2]

The demonstration that SKAP1 regulates LFA-1 adhesion was made by retroviral infection [3] and by the SKAP1 deficient mouse [4]. Additional work has implicated SKAP1 in binding to the exchange factor RasGRP1 and in regulating ERK activation in T-cells [5][6].

Interactions

SKAP1 has been shown to interact with FYN,[1][7][8] PTPRC[9] and FYB.[8][10]

References

  1. ^ a b Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B (Jul 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. doi:10.1074/jbc.272.26.16077. PMID 9195899. 
  2. ^ a b "Entrez Gene: SKAP1 src kinase associated phosphoprotein 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8631. 
  3. ^ 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. 
  4. ^ 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.
  5. ^ *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. 
  6. ^ 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.
  7. ^ Wu, Liangtang; Yu Zhenbao, Shen Shi-Hsiang (Oct. 2002). "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". J. Biol. Chem. (United States) 277 (43): 40420–7. doi:10.1074/jbc.M206023200. ISSN 0021-9258. PMID 12171928. 
  8. ^ a b Marie-Cardine, A; Hendricks-Taylor L R, Boerth N J, Zhao H, Schraven B, Koretzky G A (Oct. 1998). "Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130". J. Biol. Chem. (UNITED STATES) 273 (40): 25789–95. doi:10.1074/jbc.273.40.25789. ISSN 0021-9258. PMID 9748251. 
  9. ^ Wu, Liangtang; Fu Jun, Shen Shi-Hsiang (Apr. 2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Mol. Cell. Biol. (United States) 22 (8): 2673–86. doi:10.1128/MCB.22.8.2673-2686.2002. ISSN 0270-7306. PMC 133720. PMID 11909961. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133720. 
  10. ^ Liu, J; Kang H, Raab M, da Silva A J, Kraeft S K, Rudd C E (Jul. 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. (UNITED STATES) 95 (15): 8779–84. doi:10.1073/pnas.95.15.8779. ISSN 0027-8424. PMC 21153. PMID 9671755. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21153. 

Further reading