COMPLEX OF PHOSPHOLIPASE C GAMMA1, GADS AND AN SLP-76 MOTIF

磷脂酶 C GAMMA1、GADS 和 SLP-76 基序的复合物

• 批准号: 7602312
• 负责人: Roy A Mariuzza
• 金额: $ 0.31万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602312
• 关键词: 1,2-diacylglycerol; 76-kDa SH2 domain-containing leukocyte protein; Adaptor Signaling Protein; Binding Sites; Cell membrane; Complex; Computer Retrieval of Information on Scientific Projects Database; Diglycerides; Enzymes; Family; Funding; Grant; Inositol 1,4,5-Trisphosphate; Institution; LCP2 gene; Ligands; PLC gamma1; Peptide/MHC Complex; Phosphorylation; Production; Protein Kinase; Protein Kinase C; Protein Tyrosine Kinase; Research; Research Personnel; Resources; SH3 Domains; Second Messenger Systems; Signal Transduction; Signaling Molecule; Source; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Tyrosine; United States National Institutes of Health; release of sequestered calcium ion into cytoplasm; second messenger; src Homology Region 2 Domain

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The enzyme phospholipase C gamma1 (PLCgamma1) is essential for T cell signaling and activation. Following engagement of the T cell receptor (TCR) by MHC/peptide ligands, the transmembrane adaptor protein, linker for activation of T cells (LAT), becomes phosphorylated at multiple tyrosines by Src or Syk family protein kinases. Phosphorylation of LAT creates binding sites for the SH2 domains of other signaling molecules, notably PLCgamma1 and the soluble adaptor Gads. In addition, PLCgamma1 and Gads interact through their SH3 domains with the adaptor SLP-76. The resulting multiprotein signaling complex, comprising LAT, Gads, PLCgamma1, and SLP-76, leads to phosphorylation of PLCgamma1 by Syk tyrosine kinases. Once activated in this manner, PLCgamma1 translocates to the plasma membrane and catalyzes production of the second messengers, inositol 1,4,5-trisphosphate and diacylglycerol, which, respectively, trigger calcium flux and contribute to protein kinase C and Ras activation.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 磷脂酶C-伽马酶1(PLCGamma1)是T细胞信号转导和激活所必需的。在T细胞受体(TCR)被MHC/多肽配体结合后，跨膜适配器蛋白作为T细胞(LAT)激活的连接物，被Src或Syk家族蛋白激酶在多种酪氨酸上磷酸化。LAT的磷酸化为其他信号分子的SH2结构域创造了结合位点，特别是PLCGamma1和可溶性接头Gads。此外，PLCGamma1和Gads通过其SH3结构域与接头SLP-76相互作用。由此产生的多蛋白信号复合体，包括LAT、Gads、PLCGamma1和SLP-76，导致Syk酪氨酸激酶对PLCGamma1的磷酸化。一旦以这种方式激活，PLCGamma1就被转移到质膜上，并催化第二信使1，4，5-三磷酸肌醇和二酰甘油的产生，这两种信使分别触发了钙离子流动，促进了蛋白激酶C和RAS的激活。