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Mol Cell Biol. 2002 Apr;22(8):2673-86.

SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription.

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  • 1Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council Canada, Montreal, Quebec H4P 2R2, Canada.

Abstract

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. Mutational analysis demonstrated the pivotal role of Tyr-232 in SKAP55 in the association with CD45. In Jurkat cells, anti-CD3 antibody stimulation promoted SKAP55 tyrosine phosphorylation and translocation from the cytoplasm to the membrane. Overexpression of SKAP55 in these cells induced transcriptional activation of the IL-2 promoter, while mutant SKAP55-Y232F totally suppressed the promoter activity. Furthermore, overexpression of SKAP55-Y232F also caused the tyrosine hyperphosphorylation of Fyn with a decreased kinase activity. Thus, SKAP55 is an essential adapter to couple CD45 with the Src family kinases for dephosphorylation and, thus, positively regulates TCR signaling.

PMID:
11909961
[PubMed - indexed for MEDLINE]
PMCID:
PMC133720
Free PMC Article
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