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Article
Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation
Journal of Molecular Biology
  • Sujan Devkota, Iowa State University
  • Raji E. Joseph, Iowa State University
  • Lie Min, University of Delaware
  • D. Bruce Fulton, Iowa State University
  • Amy Andreotti, Iowa State University
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
8-28-2015
DOI
10.1016/j.jmb.2015.04.012
Abstract
Activation of the phospholipase, PLCγ1, is critical for proper T cell signaling following antigen receptor engagement. In T cells, the Tec family kinase, ITK, phosphorylates PLCγ1 at tyrosine 783 (Y783) leading to activation of phospholipase function and subsequent production of the second messengers IP3 and DAG. In this work we demonstrate that PLCγ1 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, pY173IDR, does not conform to the canonical recognition motif for an SH2 domain yet binds with significant affinity to the C-terminal SH2 domain of PLCγ1 (SH2C). The SLP-76 pY173 motif competes with the autoinhibited conformation surrounding the SH2C domain of PLCγ1 leading to exposure of the ITK recognition element on the PLCγ1 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.
Comments

This is a manuscript of an article published as Devkota, Sujan, Raji E. Joseph, Lie Min, D. Bruce Fulton, and Amy H. Andreotti. "Scaffold protein SLP-76 primes PLCγ1 for activation by ITK-mediated phosphorylation." Journal of molecular biology 427, no. 17 (2015): 2734-2747. doi: 10.1016/j.jmb.2015.04.012. Posted with permission.

Creative Commons License
Creative Commons Attribution-Noncommercial-No Derivative Works 4.0
Copyright Owner
Elsevier Ltd
Language
en
File Format
application/pdf
Citation Information
Sujan Devkota, Raji E. Joseph, Lie Min, D. Bruce Fulton, et al.. "Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation" Journal of Molecular Biology Vol. 427 Iss. 17 (2015) p. 2734 - 2747
Available at: http://works.bepress.com/amy_andreotti/27/