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Pertussis toxin‐sensitive G‐proteins inhibit fibroblast growth factor‐induced signaling in pancreatic acini
Author(s) -
Piiper Albrecht,
StryjekKaminska Danuta,
Gebhardt Ralph,
Zeuzem Stefan
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199604)167:1<52::aid-jcp6>3.0.co;2-b
Subject(s) - g protein , pertussis toxin , phospholipase c , fibroblast growth factor , receptor , signal transduction , gq alpha subunit , biology , microbiology and biotechnology , tyrosine phosphorylation , medicine , endocrinology , chemistry , biochemistry
Signal transduction of fibroblast growth factor (FGF) receptors is known to involve tyrosine phosphorylation of several substrates, including Grb2, phospholipase C‐γ, 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‐γ1 in rat pancreatic acini. Both basic fibroblast growth factor (FGF‐2) and guanosine 5′‐(γ‐O‐thio)triphosphate (GTPγS) caused an increase in inositol 1,4,5‐trisphosphate (1,4,5‐IP 3 ) production and amylase release. Combined stimulation of the acini with GTPγS 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 α‐subunit of G i ‐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 G i ‐proteins. Pretreatment of acini with pertussis toxin which inhibits G i ‐type G‐proteins abolished the inhibitory effect of GTPγS on FGF‐induced 1,4,5‐IP 3 production and amylase release, whereas the stimulatory effects of FGF‐2 and GTPγS on these parameters remained unchanged. In conclusion, these results show communication of FGF receptors and G i ‐type G‐proteins and that G i ‐type G‐proteins exert an inhibitory influence on FGF‐induced activation of phosphoinositide‐specific phospholipase C in pancreatic acinar cells. © 1996 Wiley‐Liss, Inc.