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. 1992 Jul 1;89(13):5720–5724. doi: 10.1073/pnas.89.13.5720

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

W P Hausdorff 1, J A Pitcher 1, D K Luttrell 1, M E Linder 1, H Kurose 1, S J Parsons 1, M G Caron 1, R J Lefkowitz 1
PMCID: PMC49368  PMID: 1378615

Abstract

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.

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Selected References

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