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. This year we published studies identifying paxillin as a Chk binding protein. In addition, screening of a phage display library with the Chk SH3 domain yielded a proline rich peptide that may represent a Chk SH3 ligand. Computer searches have identified possible protein candidates as Chk interaction protiens. These leads are now under investigation. Together with our continuing studies of the expression of Chk and investigation of Chk knockout mice, this work should shed light on the molecular control of macrophage and/or T cell and NK cell adherence and immune regulation.
| 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 |
