Phospholipase C gamma 1--Biochemistry and Biology

描述（由申请人提供）：本补助金申请的主要重点 是磷脂酶C-γ 1（PLC γ 1），几乎所有受体和一些 非受体酪氨酸激酶。当被激活时，这种蛋白质介导 水解磷脂酰肌醇4，5-二磷酸产生第二信使 升高Ca 2+并激活蛋白激酶C的分子。因此，PLC-gamma 1具有 在生长因子中的潜在重要作用，但尚未充分阐明 有丝分裂信号本文提出的实验的总体目标是： 应用是在生物化学水平上理解PLC γ 1 （结构/功能，膜转位和激活机制），以及 因为它在控制细胞生长的信号转导途径中的作用 即早基因的因子依赖性表达， 粘附于基质和细胞存活。最后阶段的建议 研究将使用Plcg 1“敲除”小鼠和胚胎干细胞来探索 该基因在红细胞生成和血管生成中的作用。此外，这一阶段的 该项目将采用Cre-lox系统，对Plcg 1进行有针对性的破坏 在表皮中。该申请建议使用包括以下内容的技术 生物化学、细胞生物学和分子遗传学。这些的结果 拟议的实验应该大大增加目前的理解如何 PLC γ 1参与生长因子依赖的有丝分裂。

DESCRIPTION (provided by applicant): The major focus of this grant application is phospholipase C-gamma1(PLCgamma1), a substrate of nearly all receptor and some non-receptor tyrosine kinases. When activated, this protein mediates the hydrolysis of phosphatidylinositol 4,5-bisphosphate producing second messenger molecules that elevate Ca2+ and activate protein kinase C. Hence, PLC-gamma1 has a potentially significant, but not well elucidated role in growth factor mitogenic signaling. The overall goal of the experiments proposed in this application is to understand PLCgamma1 at the biochemical level (structure/function, membrane translocation, and activation mechanism), as well as its role in signal transduction pathways that control the growth factor-dependent expression of immediate early genes, the process of cell adhesion to substrata, and cell survival. The final phase of the proposed research will use Plcg1 "knockout" mice and embryonic stem cells to explore the role of this gene in erythrogenesis and vasculogenesis. Also, this phase of the project will employ the Cre-lox system to effect a targeted disruption of Plcg1 in the epidermis. The application proposes to use techniques that encompass biochemistry, cell biology, and molecular genetics. The result of these proposed experiments should significantly increase current understanding of how PLCgamma1 participates in growth factor-dependent mitogenesis.