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: 7726245
• 负责人: Roy A Mariuzza
• 金额: $ 0.4万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726245
• 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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 磷脂酶C γ 1（PLC γ 1）是T细胞信号传导和活化所必需的。在T细胞受体（TCR）被MHC/肽配体接合之后，跨膜衔接蛋白（用于活化T细胞（LAT）的接头）在多个酪氨酸处被Src或Syk家族蛋白激酶磷酸化。LAT的磷酸化为其他信号分子的SH 2结构域产生结合位点，特别是PLC γ 1和可溶性衔接子Gads。此外，PLC γ 1和Gads通过其SH 3结构域与接头SLP-76相互作用。由此产生的多蛋白信号复合物，包括LAT，Gads，PLC γ 1，和SLP-76，导致PLC γ 1的磷酸化Syk酪氨酸激酶。一旦以这种方式激活，PLC γ 1易位到质膜并催化第二信使肌醇1，4，5-三磷酸和甘油二酯的产生，其分别触发钙流并有助于蛋白激酶C和Ras激活。