A role for cholecystokinin-stimulated protein tyrosine phosphorylation in regulated secretion by the pancreatic acinar cell

M. P. Lutz, S. L. Sutor, R. T. Abraham, L. J. Miller

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Cholecystokinin (CCK) is a gastrointestinal hormone that acts through a G protein-coupled receptor to stimulate pancreatic enzyme secretion. In this work, we demonstrate that CCK stimulation of dispersed pancreatic acini results in increased tyrosine phosphorylation of several cellular proteins. This is mediated via a calcium-dependent pathway, also activated by a phenethyl ester analogue of CCK and calcium ionophores, and by a protein kinase C-dependent cascade, also activated by the phorbol ester 12-O- tetradecanoylphorbol-13-acetate. All demonstrable stimulated tyrosine phosphorylation events were inhibited by genistein, with different subsets of proteins affected by staurosporine and H-7. The importance of tyrosine phosphorylation events in agonist-stimulated amylase secretion was studied using genistein and staurosporine as protein kinase inhibitors. Genistein inhibited the secretory response to CCK, its phenethyl ester analogue, and calcium ionophores, all known to stimulate secretion in a calcium-dependent fashion. In contrast, genistein had no effect on the secretory response to 12-O-tetradecanoylphorbol-13-acetate, suggesting that the protein kinase C- dependent tyrosine phosphorylation events were not involved in the secretory mechanism. Furthermore, CCK-induced secretion was not affected by relatively specific protein kinase C inhibition by H-7, but was decreased by staurosporine, an inhibitor of both protein kinase C and tyrosine kinase activities in these cells. These results provide evidence that acinar cell tyrosine phosphorylation is stimulated by agonists acting via calcium- dependent and protein kinase C-dependent pathways, with only the calcium- dependent tyrosine phosphorylation cascade involved in triggering hormone- induced amylase release.

Original languageEnglish (US)
Pages (from-to)11119-11124
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number15
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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