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）。在发现Chk之前，Csk是已知的唯一磷酸化Src家族激酶的保守羧基端酪氨酸并下调其催化活性的PTK。与普遍表达的Csk不同，Chk主要在造血细胞中表达。我们已经表明，Chk的表达是可诱导的T细胞和外周血单核细胞。然而，我们的研究表明，与Csk不同，Chk表达不会抑制T细胞受体功能。为了了解Csk和Chk在T细胞中的不同作用，我们从T细胞裂解物中鉴定了Chk Src同源（SH）2结构域结合蛋白。我们在这个项目上唯一的努力是建立合作，努力识别可能揭示Chk -/-小鼠表型的病理条件，以及正在进行的Chk-/-小鼠血小板功能分析。

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.