Pertussis toxin-sensitive G-proteins inhibit fibroblast growth factor-induced signaling in pancreatic acini.
Signal transduction of fibroblast growth factor (FGF) receptors is known to involve tyrosine phosphorylation of several substrates, including Grb2, phospholipase C-gamma, and phosphatidylinositol 3-kinase, whereas the role of G-proteins in FGF receptor signaling is controversial. In the present study we investigated the role of G-proteins in FGF receptor signaling in rat pancreatic acini. Immunological analysis revealed the presence of FGF receptor and phospholipase C-gamma1 in rat pancreatic acini. Both basic fibroblast growth factor (FGF-2) and guanosine 5'-(gamma-O-thio)triphosphate (GTPgammaS) caused an increase in inositol 1,4,5-trisphosphate (1,4,5-IP3) production and amylase release. Combined stimulation of the acini with GTPgammaS and FGF-2 led to a decrease of these responses as compared to the effect of the single substances. When pancreatic acini were preincubated with FGF-2 (1 nM) or vehicle (water) ADP-ribosylation of the alpha-subunit of Gi-type G-proteins by pertussis toxin was reduced in membranes prepared from FGF-2 pretreated acini as compared to control acini, suggesting functional interaction of FGF receptors with Gi-proteins. Pretreatment of acini with pertussis toxin which inhibits Gi-type G-proteins abolished the inhibitory effect of GTPgammaS on FGF-induced 1,4,5-IP3 production and amylase release, whereas the stimulatory effects of FGF-2 and GTPgammaS on these parameters remained unchanged. In conclusion, these results show communication of FGF receptors and Gi-type G-proteins and that Gi-type G-proteins exert an inhibitory influence on FGF-induced activation of phosphoinositide-specific phospholipase C in pancreatic acinar cells.
Piiper
A
A
Medical Department, University of Frankfurt, Germany.
Stryjek-Kaminska
D
D
Gebhardt
R
R
Zeuzem
S
S
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D017468:Receptors, Fibroblast Growth Factor; D010566:Virulence Factors, Bordetella; D016222:Fibroblast Growth Factor 2; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins