Tyrosine phosphorylation of G protein alpha subunits by pp60c-src

Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5720-4. doi: 10.1073/pnas.89.13.5720.


A number of lines of evidence suggest that cross-talk exists between the cellular signal transduction pathways involving tyrosine phosphorylation catalyzed by members of the pp60c-src kinase family and those mediated by guanine nucleotide regulatory proteins (G proteins). In this study, we explore the possibility that direct interactions between pp60c-src and G proteins may occur with functional consequences. Preparations of pp60c-src isolated by immunoprecipitation phosphorylate on tyrosine residues the purified G-protein alpha subunits (G alpha) of several heterotrimeric G proteins. Phosphorylation is highly dependent on G-protein conformation, and G alpha(GDP) uncomplexed by beta gamma subunits appears to be the preferred substrate. In functional studies, phosphorylation of stimulatory G alpha (G alpha s) modestly increases the rate of binding of guanosine 5'-[gamma-[35S]thio]triphosphate to Gs as well as the receptor-stimulated steady-state rate of GTP hydrolysis by Gs. Heterotrimeric G proteins may represent a previously unappreciated class of potential substrates for pp60c-src.

Publication types

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

MeSH terms

  • Animals
  • Fluorides / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotides / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine
  • Protein Conformation
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Guanine Nucleotides
  • Phosphoproteins
  • Phosphotyrosine
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Tyrosine
  • Proto-Oncogene Proteins pp60(c-src)
  • GTP-Binding Proteins
  • Fluorides