Inhibition of amylase secretion from differentiated AR4-2J pancreatic acinar cells by an actin cytoskeleton controlled protein tyrosine phosphatase activity

Disruption of the actin cytoskeleton in AR4-2J pancreatic acinar cells led to an increase in cytosolic protein tyrosine phosphatase activity, abolishe d bombesin-induced tyrosine phosphorylation and reduced bombesin-induced am ylase secretion by about 45%, Furthermore, both tyrosine phosphorylation an d amylase secretion induced by phorbol ester-induced activation of protein kinase C were abolished. An increase in the cytosolic free Ca2+ concentrati on by the Ca2+ ionophore A23187 had no effect on tyrosine phosphorylation b ut induced amylase release. Only when added together with phorbol ester, th e same level of amylase secretion as with bombesin was reached. This amylas e secretion was inhibited by about 40% by actin cytoskeleton disruption sim ilar to that induced by bombesin, We conclude that actin cytoskeleton-contr olled protein tyrosine phosphatase activity downstream of protein kinase C activity regulates tyrosine phosphorylation which in part is involved in bo mbesin-stimulated amylase secretion. (C) 1999 Federation of European Bioche mical Societies.