Differential involvement of Src family kinases in pervanadate-mediated responses in rat myometrial cells.
We previously described that pervanadate, a potent tyrosine phosphatase inhibitor, induced contraction of rat myometrium via phospholipase (PL) C-gamma1 activation [Biol Reprod 54 (1996) 1383]. In this study, we found that pervanadate induced tyrosine phosphorylation of the platelet-derived growth factor (PDGF)-beta receptor, interaction of the phosphorylated PDGF receptor with the phosphorylated PLC-gamma1, production of inositol phosphates (InsPs), extracellular signal-regulated kinase (ERK) activation and DNA synthesis. All these responses were insensitive to PDGF receptor kinase inhibition or PDGF receptor down-regulation. We showed that Src family kinases were activated by pervanadate, and that InsPs production and phosphorylation of both PLC-gamma1 and the PDGF receptor were blocked by PP1, an Src inhibitor. In contrast, the stimulation of ERK by pervanadate was totally refractory to PP1. These results demonstrated that the activation of Src by pervanadate is involved in PLC-gamma1/InsPs signalling but does not play a major role in ERK activation.
Boulven
Isaline
I
Laboratoire de Signalisation et Régulations Cellulaires, Centre National de la Recherche Scientifique (CNRS) UMR 8619, Bâtiment 430, Université de Paris-Sud, 91405 Orsay cedex, France.
Robin
Philippe
P
Desmyter
Christine
C
Harbon
Simone
S
Leiber
Denis
D
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007295:Inositol Phosphates / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D007527:Isoenzymes; C076715:pervanadate; D019000:Phosphotyrosine; D014638:Vanadates; D004247:DNA; D020797:Receptor, Platelet-Derived Growth Factor beta; D016392:Proto-Oncogene Proteins pp60(c-src); D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma