Open AccessTyrosine phosphorylation of G protein alpha subunits by pp60c-src.
Author(s) -
William P. Hausdorff,
Julie A. Pitcher,
Deirdre K. Luttrell,
Maurine E. Linder,
Hitoshi Kurose,
Sarah J. Parsons,
Marc G. Caron,
Robert J. Lefkowitz
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.13.5720
Subject(s) - heterotrimeric g protein , g alpha subunit , g protein , guanosine , phosphorylation , biology , tyrosine phosphorylation , biochemistry , tyrosine , sh2 domain , immunoprecipitation , gtp binding protein regulators , g beta gamma complex , signal transduction , protein subunit , gene
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.