Chk, a Csk family tyrosine protein kinase, exhibits Csk-like activity in fibroblasts, but not in an antigen-specific T-cell line.
The Csk family of tyrosine protein kinases comprises two members named Csk and Chk. These enzymes phosphorylate the carboxyl-terminal tyrosine of Src-related kinases in vitro, thereby repressing their activity. Csk has been found to be necessary for normal embryonic development, and to be a potent negative regulator of antigen receptor signaling in T-lymphocytes. As the functions of Chk in mammalian cells are not known, we examined its ability to carry out Csk-like functions in vivo. Like p50csk, Chk reduced the elevated phosphotyrosine levels and the augmented activity of Src family kinases in Csk-deficient fibroblasts. Contrary to Csk, however, Chk was inefficient at repressing antigen receptor-induced signals in a T-cell line (BI-141). We also noted that Chk, but not Csk, failed to stably associate with cellular membranes following addition of a membrane targeting signal to its amino terminus. This observation suggested that Chk may contain dominant targeting sequences disallowing its recruitment to cellular membranes. Hence, these data demonstrate that Chk can mediate some, but not all, Csk-related functions in vivo. Moreover, they suggest that the "restricted" function of Chk may relate at least in part to its inability to be recruited to certain cellular locales.
Davidson
D
D
McGill Cancer Centre, McGill University, Montréal, Canada.
Chow
L M
LM
Veillette
A
A
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D000071877:Checkpoint Kinase 1; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src); D012190:Retroviridae; D013601:T-Lymphocytes / Q000201:enzymology*; D018909:src Homology Domains
D018076:DNA, Complementary; D011494:Protein Kinases; C086603:Matk protein, mouse; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D000071877:Checkpoint Kinase 1