Keeping the (Kinase) Party Going: SLP-76 and ITK Dance to the Beat

Sci. STKE, 24 July 2007
Vol. 2007, Issue 396, p. pe39
DOI: 10.1126/stke.3962007pe39

Keeping the (Kinase) Party Going: SLP-76 and ITK Dance to the Beat

  1. Qian Qi and
  2. Avery August*
  1. Center for Molecular Immunology and Infectious Disease, Immunology and Infectious Disease Graduate Program, and Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  1. *Corresponding author. E-mail, avery{at}psu.edu

Abstract

The Tec-family protein tyrosine kinase IL-2–inducible T cell kinase (ITK) mediates T cell activation, as does the adaptor protein SLP-76 (SH2-domain–containing leukocyte protein of 76 kD), which forms a complex with ITK and other intracellular signaling enzymes. One of these enzymes is phospholipase C–γ1 (PLC-γ1), which mediates T cell receptor (TCR)–stimulated intracellular calcium mobilization leading to the activation of transcription factors such as nuclear factor of activated T cells. The Src-family tyrosine kinase Lck and the Syk-family tyrosine kinase ζ chain–associated protein kinase of 70 kD (ZAP-70), together with ITK, are necessary for the phosphorylation of PLC-γ1 in response to TCR stimulation. ITK is thought to phosphorylate a specific tyrosine residue of PLC-γ1 that is required for its activation. The mechanism of activation of ITK appears to involve the interaction between SLP-76 and ITK, which not only initiates ITK activity but is also important to maintain the kinase activity of ITK. This suggests that SLP-76 acts as more than a neutral adaptor in mediating T cell activation; SLP-76 also directly influences the kinase activity of ITK, allowing ITK to phosphorylate PLC-γ1.

Citation:

Q. Qi and A. August, Keeping the (Kinase) Party Going: SLP-76 and ITK Dance to the Beat. Sci. STKE 2007, pe39 (2007).

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