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

Molecular and Cellular Biology
Liangtang WuShi-Hsiang Shen

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.

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Citations

Dec 26, 2013·The Journal of Cell Biology·Michael J OphirStephen C Bunnell
Jun 9, 2005·The Journal of Experimental Medicine·Eun-Kyeong JoChristopher E Rudd
Jul 25, 2007·Molecular and Cellular Biology·Hongyan WangChristopher E Rudd
Nov 5, 2002·Annual Review of Immunology·Michelle L HermistonArthur Weiss
May 26, 2007·Molecular Immunology·Krikor BijianShi-Hsiang Shen
Apr 3, 2003·Immunological Reviews·Erik J Peterson
Jan 21, 2006·Immunology·Nick Holmes
Mar 26, 2003·Nature Immunology·Hongyan WangChristopher E Rudd
Aug 15, 2002·The Journal of Biological Chemistry·Zhenbao YuShi-Hsiang Shen
Apr 26, 2005·The Journal of Biological Chemistry·Yanping HuangRonald L Wange
Aug 13, 2002·The Journal of Biological Chemistry·Liangtang WuShi-Hsiang Shen
Jan 14, 2017·Microbiology Spectrum·Elsa Du Bruyn, Robert John Wilkinson

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