Cloning and Characterization of Protein Tyrosine Kinases

蛋白酪氨酸激酶的克隆和表征

• 批准号: 6950574
• 负责人: Daniel W. McVicar
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6950574
• 关键词: T cell receptor; T lymphocyte; binding proteins; enzyme activity; genetically modified animals; laboratory mouse; leukocyte activation /transformation; molecular cloning; natural killer cells; protein structure function; protein tyrosine kinase

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.

该项目涉及对从自然杀伤细胞克隆的蛋白酪氨酸激酶 (PTK) 进行持续表征。该项目的主要重点是研究与羧基末端 Src 激酶 (Csk) 具有显着同源性的 PTK； Csk 同源激酶 Chk（以前称为 Lsk）。在 Chk 发现之前，Csk 是唯一已知能够磷酸化 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。与普遍表达的 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 细胞裂解物中鉴定出 Chk Src 同源 (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，以鉴定可能揭示 Chk -/- 小鼠表型的病理状况。