Skip to main content
Article
A Remote Substrate Docking Mechanism for the Tec Family Tyrosine Kinases
Biochemistry
  • Raji E. Joseph, Iowa State University
  • Lie Min, Iowa State University
  • Ruo Xu, Iowa State University
  • Eli D. Musselman, Buena Vista University
  • Amy H. Andreotti, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
4-1-2007
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.

Rights
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
Citation Information
Raji E. Joseph, Lie Min, Ruo Xu, Eli D. Musselman, et al.. "A Remote Substrate Docking Mechanism for the Tec Family Tyrosine Kinases" Biochemistry Vol. 46 Iss. 18 (2007) p. 5595 - 5603
Available at: http://works.bepress.com/amy_andreotti/12/