Beta 1 integrin ligation stimulates tyrosine phosphorylation of phospholipase C gamma 1 and elevates intracellular Ca2+ in pancreatic acinar cells.

We have recently reported increased tyrosine (TYR) phosphorylation of a number of pancreatic acinar cell proteins following antibody ligation of beta 1 integrins (Wrenn and Herman, Biochem, Biophys. Res. Commun. 208, 1995, 978-984). Concurrent with this TYR phosphorylation was a marked activation of protein kinase C (PKC). This led us to investigate phospholipase C gamma 1 (PLC gamma 1), a key enzyme responsible for diacylglycerol generation, as a target for integrin-mediated TYR phosphorylation. Staining with antiphosphotyrosine antibodies revealed increased TYR phosphorylation of immunoprecipitated PLC gamma 1 prepared from beta 1 integrin-ligated acinar cells. Subsequent stripping and reprobing of Western blots with polyclonal anti-PLC gamma 1 was confirmatory. Over this same time period, intracellular [Ca2+] increased from < 100 nM to 600 nM, further suggesting a functional relevance of integrin-linked phosphorylation as a regulatory mechanism in exocrine pancreas.