Src kinase pathways in extracellular Ca(2+)-dependent pancreatic enzyme secretion.

We investigated the functional roles of Src kinase pathways in rat pancreatic acinar cells. CCK-8 dose-dependently increased Src kinase activities by a mechanism that was sensitive to herbimycin A. CCK-8 enhanced protein tyrosine kinase (PTK) activities when the synthetic Src peptide was used as a substrate. Increased PTK activities, sustained Ca2+ entry, and amylase secretion, all stimulated by CCK-8, were abolished by eliminating extracellular Ca2+ ([Ca2+]o). CCK-8 caused tyrosine phosphorylation of three major proteins: 60 KDa, 85 KDa, and 105 KDa. The elimination of [Ca2+]o prevented the tyrosine phosphorylations of p60 and p105, but not p85. Therefore, the p60 Src kinase and the p105 kinase, referred to as "Src kinase kinase', may be involved in [Ca2+]o-dependent pancreatic exocytosis.