Open AccessSKAP55 Coupled with CD45 Positively Regulates T-Cell Receptor-Mediated Gene Transcription
Author(s) -
Liangtang Wu,
Jun Fu,
Shi-Hsiang Shen
Publication year - 2002
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.22.8.2673-2686.2002
Subject(s) - biology , jurkat cells , fyn , t cell receptor , tyrosine kinase , tyrosine protein kinase csk , microbiology and biotechnology , phosphoprotein , kinase , tyrosine phosphorylation , phosphorylation , proto oncogene tyrosine protein kinase src , signal transduction , t cell , sh2 domain , genetics , immune system
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.