Fibroblast growth factor potentiates receptor- and nonreceptor-mediated stimulation of adenylate cyclase in hamster fibroblasts.
Basic fibroblast growth factor (FGF) has no effect alone on the basal cAMP synthesis in Chinese hamster fibroblasts (CCL39) but it potentiates (by up to 50%) the stimulation of adenylate cyclase by prostaglandin E1, cholera toxin or forskolin. This potentiating effect is not abolished by pretreatment of the cells with pertussis toxin, which indicates that it is not due to the withdrawal of a tonic inhibition of adenylate cyclase by the pertussis toxin-sensitive inhibitory GTP-binding protein (Gi). Therefore, we conclude that FGF enhances the activation of adenylate cyclase by the stimulatory GTP-binding protein (Gs). Although activation of protein kinase C in CCL39 cells results in a similar potentiation of cAMP production, we provide evidence that the effect of FGF is not mediated by protein kinase C, since (1) the potentiating effects of FGF and phorbol esters are additive and (2) FGF effect persists after down-regulation of protein kinase C. A role of FGF-induced rise in cytoplasmic Ca2+ can also be ruled out because the FGF effect is not mimicked by a Ca2+ ionophore and it persists in Ca2(+)-free medium. Since a similar potentiating effect on cAMP production is elicited by epidermal growth factor, a mitogen known to activate a receptor tyrosine kinase, we suggest that the FGF effect on adenylate cyclase might be mediated by the tyrosine kinase activity that is very likely to be associated with FGF receptors.
Magnaldo
I
I
CNRS, Université de Nice, France.
Pouyssegur
J
J
Paris
S
S
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D007328:Insulin; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D010566:Virulence Factors, Bordetella; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium