Src family tyrosine kinases associate with and phosphorylate CTLA-4 (CD152).
CTLA-4 (CD152) transduces inhibitory signals for T cell activation. Phosphorylation and dephosphorylation of tyrosine residue (Y)-165 in the cytoplasmic region of CTLA-4 play an important role in the signal transduction and in the cell surface. While signaling molecules such as SHP-2 and the p85 subunit of PI3 kinase associate with ... this tyrosine residue through SH2 domains upon phosphorylation, the adapter complex AP-2 interacts with the same tyrosine when dephosphorylated, leading to clathrin-mediated endocytosis of CTLA-4. We searched for the tyrosine kinase responsible for the phosphorylation of CTLA-4. Src family tyrosine kinases Fyn, Lyn, and Lck associate with CTLA-4 and phosphorylate both Y-165 and Y-182 that are mainly responsible for interaction with Fyn through its SH2 domain. SHP-2 associates with CTLA-4, in a Fyn-dependent manner. Our observations show that src family tyrosine kinases associate with and phosphorylate CTLA-4 and thereby have an important role in the signal transduction and the endocytosis of CTLA-4.
Mesh Terms:
Animals, Antigens, CD, Antigens, Differentiation, COS Cells, Cell Line, Endocytosis, Immunoblotting, Immunoconjugates, Immunosorbent Techniques, Phosphorylation, Phosphotyrosine, Protein-Tyrosine Kinases, Signal Transduction, Sulfhydryl Compounds, Transfection, src-Family Kinases
Animals, Antigens, CD, Antigens, Differentiation, COS Cells, Cell Line, Endocytosis, Immunoblotting, Immunoconjugates, Immunosorbent Techniques, Phosphorylation, Phosphotyrosine, Protein-Tyrosine Kinases, Signal Transduction, Sulfhydryl Compounds, Transfection, src-Family Kinases
Biochem. Biophys. Res. Commun.
Date: Aug. 19, 1998
PubMed ID: 9712716
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