SKAP1

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Src kinase associated phosphoprotein 1
PDB rendering based on 1u5d.
Available structures: 1u5d
Identifiers
Symbol(s) SKAP1; SCAP1; SKAP55
External IDs OMIM: 604969 MGI: 1925723 HomoloGene: 2764
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 8631 78473
Ensembl ENSG00000141293 ENSMUSG00000057058
Uniprot Q86WV1 Q3UUV5
Refseq NM_001075099 (mRNA)
NP_001068567 (protein)		 NM_001033186 (mRNA)
NP_001028358 (protein)
Location Chr 17: 43.57 - 43.86 Mb Chr 11: 96.28 - 96.58 Mb
Pubmed search [1] [2]

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].

[edit] References

  1. ^ a b 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.

[edit] 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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