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PMID: 1378615 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 13 ·1992-07-01 ·Pages 5720-4

Hausdorff WP, Pitcher JA, Luttrell DK, Linder ME, Kurose H, Parsons SJ, Caron MG, Lefkowitz RJ

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.

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,metabolism
Chemicals
Guanine Nucleotides Phosphoproteins Phosphotyrosine Guanosine 5'-O-(3-Thiotriphosphate) Tyrosine Proto-Oncogene Proteins pp60(c-src) GTP-Binding Proteins Fluorides
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Hausdorff W P
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Pitcher J A
Luttrell D K
Linder M E
Kurose H
Parsons S J
Caron M G
Lefkowitz R J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.13.5720
Published
1992-07-01
Pages
5720-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49368
Subset
IM
Grants
NIGMS NIH HHS · GM34497 · United States
NHLBI NIH HHS · HL16037 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.13.5720 PMC Full Text View journal details
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