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Article
SH2-Dependent Autophosphorylation within the Tec Family Kinase Itk
Journal of Molecular Biology
  • Raji E. Joseph, Iowa State University
  • Andrew Severin, Iowa State University
  • Lie Min, Iowa State University
  • D. Bruce Fulton, Iowa State University
  • Amy H. Andreotti, Iowa State University
Document Type
Article
Disciplines
Publication Version
Accepted Manuscript
Publication Date
8-7-2009
DOI
10.1016/j.jmb.2009.06.023
Abstract
The Tec family kinase, Itk (interleukin-2 tyrosine kinase), undergoes an in cis autophosphorylation on Y180 within its Src homology 3 (SH3) domain. Autophosphorylation of the Itk SH3 domain by the Itk kinase domain is strictly dependent on the presence of the intervening Src homology 2 (SH2) domain. A direct docking interaction between the Itk kinase and SH2 domains brings the Itk SH3 domain into the active site where Y180 is then phosphorylated. We now identify the residues on the surface of the Itk SH2 domain responsible for substrate docking and show that this SH2 surface mediates autophosphorylation in the full-length Itk molecule. The canonical phospholigand binding site on the SH2 domain is not involved in substrate docking, instead the docking site consists of side chains from three loop regions (AB, EF and BG) and part of the βD strand. These results are extended into Btk (Bruton's tyrosine kinase), a Tec family kinase linked to the B-cell deficiency X-linked agammaglobulinemia (XLA). Our results suggest that some XLA-causing mutations might impair Btk phosphorylation.
Comments

This article is from Journal of Molecular Biology 391 (2009): 164–177, doi:10.1016/j.jmb.2009.06.023. Posted with permission.

Copyright Owner
Elsevier Ltd.
Language
en
File Format
application/pdf
Citation Information
Raji E. Joseph, Andrew Severin, Lie Min, D. Bruce Fulton, et al.. "SH2-Dependent Autophosphorylation within the Tec Family Kinase Itk" Journal of Molecular Biology Vol. 391 Iss. 1 (2009) p. 164 - 177
Available at: http://works.bepress.com/amy_andreotti/17/