CHK, A CSK FAMILY TYROSINE PROTEIN-KINASE, EXHIBITS CSK-LIKE ACTIVITYIN 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 tyrosi ne 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 kno wn, we examined its ability to carry out Csk-like functions in vivo. L ike p50(csk), 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 r eceptor-induced signals in a T-cell line (BI-141). We also noted that Chk, but not Csk, failed to stably associate with cellular membranes f ollowing addition of a membrane targeting signal to its amino terminus . This observation suggested that Chk may contain dominant targeting s equences disallowing its recruitment to cellular membranes. Hence, the se data demonstrate that Chk can mediate some, but not all, Csk relate d functions in vivo. Moreover, they suggest that the ''restricted'' fu nction of Chk may relate at least in part to its inability to be recru ited to certain cellular locales.