Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck, fyn, and c-src tyrosine protein kinases.
Expression of the CD45 tyrosine protein phosphatase is required for the response of functional lymphocytes to stimulation through the antigen receptor. One or more of its substrates may therefore be essential for signal transduction during lymphocyte activation. We have studied the phosphorylation of the closely related lck, fyn, and c-src tyrosine protein kinases in leukemic murine T-cell lines that have lost the expression of CD45. The phosphorylation of the lck kinase at an inhibitory site of tyrosine phosphorylation, Tyr-505, was increased by two-, six-, and eightfold in three different cell lines. Phosphorylation of the fyn kinase at the homologous site, Tyr-531, was unaltered in one of these cell lines, but increased by 2.5-fold in the two others. The phosphorylation of p60c-src at the homologous tyrosine was essentially unchanged in the one CD45-negative cell line in which it was examined. The expression of CD45 therefore regulates the phosphorylation and potentially the activity of the lck and fyn tyrosine protein kinases, but the effect on the lck kinase is much greater than on the fyn kinase. This finding and the observation that CD45 had no effect on the phosphorylation of p60c-src suggest that CD45 exhibits polypeptide substrate specificity in vivo. Additionally, these findings are consistent with the hypothesis that the unresponsiveness of CD45-negative lymphoid cells to antigenic stimulation is due largely to hyperphosphorylation of the lck kinase.
Hurley
T R
TR
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186.
Hyman
R
R
Sefton
B M
BM
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D007942:Leukemia, Experimental / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D010449:Peptide Mapping; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases
D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases