Scaffold Protein SLP-76 Primes PLC?1 for Activation by ITK-Mediated Phosphorylation.

ABSTRACT: Activation of the phospholipase, PLC?1, is critical for proper T cell signaling following antigen receptor engagement. In T cells, the Tec family kinase, interleukin-2-induced tyrosine kinase (ITK), phosphorylates PLC?1 at tyrosine 783 (Y783) leading to activation of phospholipase function and subsequent production of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. In this work, we demonstrate that PLC?1 can be primed for ITK-mediated phosphorylation on Y783 by a specific region of the adaptor protein, SLP-76. The SLP-76 phosphotyrosine-containing sequence, pY(173)IDR, does not conform to the canonical recognition motif for an SH2 domain yet binds with significant affinity to the C-terminal SH2 domain of PLC?1 (SH2C). The SLP-76 pY(173) motif competes with the autoinhibited conformation surrounding the SH2C domain of PLC?1 leading to exposure of the ITK recognition element on the PLC?1 SH2 domain and release of the target tyrosine, Y783. These data contribute to the evolving model for the molecular events occurring early in the T cell activation process.

SUBMITTER: Devkota S 

PROVIDER: S-EPMC4540666 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature