Pertussis toxin-sensitive G-proteins inhibit fibroblast growth factor-induced signaling in pancreatic acini

✍ Scribed by Albrecht Piiper; Danuta Stryjek-Kaminska; Ralph Gebhardt; Stefan Zeuzem

• Book ID: 102654906
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 900 KB
• Volume: 167
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199604)167:1<52::aid-jcp6>3.0.co;2-b

✦ Synopsis

Signal transduction of fibroblast growth factor (FGF) receptors is known to involve tyrosine phosphorylation of several substrates, including Grb2, phospholipase Cy, 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 Gproteins in FGF receptor signaling in rat pancreatic acini. Immunological analysis revealed the presence of FGF receptor and phospholipase C-yl in rat pancreatic acini. Both basic fibroblast growth factor (FGF-2) and guanosine 5'-(y-0-thio)triphosphate (GTPyS) caused an increase in inositol 1,4,5-trisphosphate (1 ,4,5-IP3) production and amylase release. Combined Stimulation of the acini with CTP@ 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 a-subunit of Gi-type C-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 (2,-proteins. Pretreatment of acini with pertussir toxin which inhibits G,type G-proteins abolished the inhibitory effect of G T V o n FGF-induced 1 ,4,5-IP3 production and amylase release, whereas the stirnulatory effects of FGF-2 and GTPyS on these parameters remained unchanged. In conclusion, these results show communication of FGF receptors and Gi-type G-proteins and that G,-type G-proteins exert an inhibitory influence on FGF-induced activation of phosphoinositidespecific phospholipase C in pancreatic acinar cells. (9 1996 Wiley-Liss, inc.