Identification of a molecular recognition role for the activation loop phosphotyrosine of the SRC tyrosine kinase

J Am Chem Soc. 2005 Feb 16;127(6):1600-1. doi: 10.1021/ja047957c.

Abstract

A human cDNA phage display library screen, using a phosphopeptide designed to mimic the activation loop phosphotyrosine of the Src tyrosine kinase, has identified the N-terminal SH2 domain of the p85 regulatory subunit of phosphatidyl inositol-3 kinase (PI3K) as an interacting recognition domain. Activation loop phosphorylation is known to play a conformational role in kinase activation, but is largely not thought to play a role in protein/protein recognition. Affinity chromatography and biochemical evaluation in mouse fibroblast cells has confirmed the dependence of this interaction on both the Src activation loop phosphotyrosine and the N-terminal SH2 domain of PI3K.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biotin / analogs & derivatives
  • Biotin / metabolism
  • Enzyme Activation
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Phosphatidylinositol 3-Kinases / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphopeptides / chemistry
  • Phosphopeptides / metabolism
  • Phosphotyrosine / analogs & derivatives
  • Phosphotyrosine / metabolism*
  • src Homology Domains
  • src-Family Kinases / chemistry
  • src-Family Kinases / metabolism*

Substances

  • Phosphopeptides
  • Phosphotyrosine
  • Biotin
  • Phosphatidylinositol 3-Kinases
  • src-Family Kinases