SIGNAL TRANSDUCTION FROM THE T-CELL ANTIGEN RECEPTOR

描述（改编自申请人的摘要）： 将细胞表面配体-受体相互作用与受调控的 细胞功能的变化仅被部分理解。 t细胞 抗原受体（TCR）是多聚体复合物，其包括CD 3 作为主要识别和信号转导的复合物 在特定的T细胞活化过程中。 TCR的触发， 活化配体刺激多效性活化反应， 在细胞生长和分化中。 原型早期（分钟） 对TCR连接的应答是来自TCR的细胞质颗粒的胞吐作用。 溶细胞性T淋巴细胞（CTL）。 该项目的长期目标是确定 跨膜信号产生和增殖由TCR连接启动。 最近的研究表明，一个未定义的蛋白酪氨酸激酶作为 来自配体结合TCR的近端信号转导元件。 这种TCR偶联蛋白酪氨酸激酶的底物是磷酸肌醇， 特异性磷脂酶C（PLC-γ 1）。 本提案的具体目标 （1）鉴定蛋白酪氨酸激酶， 将TCR连接与PLC-γ 1的酪氨酸磷酸化偶联;（2） 确定改变的PLC-γ 1同工酶表达对信号的影响 通过TCR的转导;和（3）检查蛋白质的作用， TCR依赖性颗粒胞吐中酪氨酸激酶激活和p21 ras 溶细胞性T细胞 研究人员表示，这一结果 这项研究应该为跨膜信号传导机制提供新的见解 参与正常细胞生长和细胞转化。

DESCRIPTION (Adapted from applicant's abstract): The cascade of molecular events that link cell surface ligand-receptor interactions to regulated changes in cellular functions are only partially understood. The T-cell antigen receptor (TCR) is a multimeric complex, which includes the CD3 complex that serves as the primary recognition and signal-transducing element during specific T-cell activation. Triggering of the TCR by activating ligands stimulates a pleiotropic activation response culminating in cell growth and differentiation. A prototypical early (minutes) response to TCR ligation is the exocytosis of cytoplasmic granules from cytolytic T-lymphocytes (CTL). The long-term goals of this project are to define the mechanisms of transmembrane signal generation and propagation initiated by TCR ligation. Recent studies indicate that an undefined protein tyrosine kinase serves as the proximal signal-transducing element from ligand-bound TCR.A critical substrate for this TCR-coupled protein tyrosine kinase is phosphoinositide- specific phospholipase C (PLC-gamma1). The specific aims of this proposal are the following: (1) To identify the protein tyrosine kinase that couples TCR-ligation to the tyrosine phosphorylation of PLC-gamma1; (2) to determine the effect of altered PLC-gamma1 isozyme expression on signal transduction through the TCR; and (3) to examine the role of protein tyrosine kinase activation and p21ras in TCR-dependent granule exocytosis in cytolytic T-cells. The investigator indicates that the results of this study should offer novel insights into transmembrane signalling mechanisms involved in both normal cell growth and cellular transformation.