This project involves the continued characterization of protein tyrosine kinases (PTK) cloned from natural killer cells. The primary emphasis of this project is the study of a PTK that has significant homology to the carboxyl-terminal Src kinase (Csk); the Csk homolgous kinase, Chk (previously known as Lsk). Before the discovery of Chk, Csk was the only PTK known to phosphorylate the conserved carboxyl-terminal tyrosine of Src family kinases and down-regulate their catalytic activity. Unlike Csk, which is ubiquitously expressed, Chk is expressed primarily in hematopoietic cells. We have shown Chk expression to be inducible in both T cells and peripheral blood monocytes. However, our studies have shown that unlike Csk, Chk expression does not inhibit T cell receptor function. In an effort to understand the different roles of Csk and Chk in T cells, we have identified Chk Src homology (SH)2 domain binding proteins from T cell lysates. Our only efforts on this project are the establishment of collaborations in an effort to identify a pathological condition that may reveal a phenotype in the Chk -/- mice and the ongoing analysis of platelet function in Chk-/- mice.
| Taylor, L S; Paul, S P; McVicar, D W (2000) Paired inhibitory and activating receptor signals. Rev Immunogenet 2:204-19 |
| Grgurevich, S; Mikhael, A; McVicar, D W (1999) The Csk homologous kinase, Chk, binds tyrosine phosphorylated paxillin in human blastic T cells. Biochem Biophys Res Commun 256:668-75 |
