Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.
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.
Hausdorff
W P
WP
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Pitcher
J A
JA
Luttrell
D K
DK
Linder
M E
ME
Kurose
H
H
Parsons
S J
SJ
Caron
M G
MG
Lefkowitz
R J
RJ
D000818:Animals; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011487:Protein Conformation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D006150:Guanine Nucleotides; D010750:Phosphoproteins; D019000:Phosphotyrosine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D019204:GTP-Binding Proteins; D005459:Fluorides