This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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