Document Type

Article

Publication Version

Published Version

Publication Date

4-2007

Journal or Book Title

Biochemistry

Volume

46

Issue

18

First Page

5595

Last Page

5603

DOI

10.1021/bi700127c

Abstract

During T cell signaling, Itk selectively phosphorylates a tyrosine within its own SH3 domain and a tyrosine within PLCγ1. We find that the remote SH2 domain in each of these substrates is required to achieve efficient tyrosine phosphorylation by Itk and extend this observation to two other Tec family kinases, Btk and Tec. Additionally, we detect a stable interaction between the substrate SH2 domains and the kinase domain of Itk and find that addition of specific, exogenous SH2 domains to the in vitro kinase assay competes directly with substrate phosphorylation. On the basis of these results, we show that the kinetic parameters of a generic peptide substrate of Itk are significantly improved via fusion of the peptide substrate to the SH2 domain of PLCγ1. This work is the first characterization of a substrate docking mechanism for the Tec kinases and provides evidence of a novel, phosphotyrosine-independent regulatory role for the ubiquitous SH2 domain.

Comments

Reprinted (adapted) with permission from Biochemistry 46 (2007: 5595, doi:10.1021/bi700127c. Copyright 2007 American Chemical Society.

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One-time permission is granted only for the use specified in your request. No additional uses are granted (such as derivative works or other editions). For any other uses, please submit a new request.

Copyright Owner

American Chemical Society

Language

en

File Format

application/pdf

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