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

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.
Mesh Terms:
Antibodies, Antigens, CD3, Antigens, CD45, Binding Sites, Biological Transport, Active, Cell Membrane, Cytoplasm, Humans, Interleukin-2, Jurkat Cells, Mutagenesis, Site-Directed, Phosphoproteins, Phosphorylation, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Receptors, Antigen, T-Cell, Recombinant Proteins, Signal Transduction, Substrate Specificity, T-Lymphocytes, Transcription, Genetic, Two-Hybrid System Techniques, Tyrosine
Mol. Cell. Biol.
Date: Apr. 01, 2002
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