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Molecular and Cellular Biology, April 2002, p. 2673-2686, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2673-2686.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

SKAP55 Coupled with CD45 Positively Regulates T-Cell Receptor-Mediated Gene Transcription

Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council Canada, Montreal, Quebec H4P 2R2, and Department of Medicine, McGill University, Montreal, Quebec H3G 1A4, Canada

Received 18 September 2001/ Returned for modification 30 November 2001/ Accepted 15 January 2002

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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