SKAP55 Coupled with CD45 Positively Regulates T-Cell Receptor-Mediated Gene Transcription
Copyright policy )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.
- McGill University Canada
- National Research Council Canada Canada
- Biotechnology Research Institute Canada
- National Academies of Sciences, Engineering, and Medicine United States
Cytoplasm, Binding Sites, CD3 Complex, Cell Membrane, Receptors, Antigen, T-Cell, Biological Transport, Active, Phosphoproteins, Proto-Oncogene Proteins c-fyn, Antibodies, Recombinant Proteins, Protein Structure, Tertiary, Jurkat Cells, Proto-Oncogene Proteins, Mutagenesis, Site-Directed, Humans, Interleukin-2, Leukocyte Common Antigens, Phosphorylation, Promoter Regions, Genetic, Signal Transduction
Cytoplasm, Binding Sites, CD3 Complex, Cell Membrane, Receptors, Antigen, T-Cell, Biological Transport, Active, Phosphoproteins, Proto-Oncogene Proteins c-fyn, Antibodies, Recombinant Proteins, Protein Structure, Tertiary, Jurkat Cells, Proto-Oncogene Proteins, Mutagenesis, Site-Directed, Humans, Interleukin-2, Leukocyte Common Antigens, Phosphorylation, Promoter Regions, Genetic, Signal Transduction
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