Cloning and Characterization of Protein Tyrosine Kinases

该项目涉及从自然杀伤细胞克隆的蛋白酪氨酸激酶（PTK）的持续表征。该项目的主要重点是研究与羧基末端Src激酶（Csk）具有显著同源性的PTK；Csk同源激酶，Chk（以前称为Lsk）。在Chk被发现之前，Csk是已知的唯一一个磷酸化Src家族激酶的保守羧基末端酪氨酸并下调其催化活性的PTK。与无处不在表达的Csk不同，Chk主要在造血细胞中表达。我们已经证明Chk表达在T细胞和外周血单核细胞中都是可诱导的。然而，我们的研究表明，与Csk不同，Chk的表达并不抑制T细胞受体的功能。为了了解Csk和Chk在T细胞中的不同作用，我们从T细胞裂解物中鉴定出Chk Src同源性（SH）2结构域结合蛋白。我们在这个项目上的唯一努力是建立合作关系，努力确定可能揭示Chk -/-小鼠表型的病理状况。

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.