SKAP1

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Src kinase associated phosphoprotein 1
Protein SKAP1 PDB 1u5d.png
PDB rendering based on 1u5d.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SKAP1 ; SCAP1; SKAP55
External IDs OMIM604969 MGI1925723 HomoloGene2764 GeneCards: SKAP1 Gene
RNA expression pattern
PBB GE SKAP1 205790 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8631 78473
Ensembl ENSG00000141293 ENSMUSG00000057058
UniProt Q86WV1 Q3UUV5
RefSeq (mRNA) NM_001075099 NM_001033186
RefSeq (protein) NP_001068567 NP_001028358
Location (UCSC) Chr 17:
46.21 – 46.51 Mb
Chr 11:
96.46 – 96.76 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[edit]

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

References[edit]

  1. ^ a b Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B (July 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". 
  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 (October 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 (October 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 (April 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. 
  10. ^ Liu, J; Kang H, Raab M, da Silva A J, Kraeft S K, Rudd C E (July 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. 

Further reading[edit]