Phospholipid-sensitive calcium-dependent protein kinase and its endogenous substrate proteins in rat pancreatic acinar cells

Phospholipid-sensitive Ca²⁺-dependent protein kinase and its endogenous substrate proteins were examined in acinar cells from rat pancreas. The enzyme was clearly demonstrable by DEAE-cellulose chromatography of acinar cell extract. At least four endogenous substrate proteins (M_r = 38K, 30K, 22K and 15K) for this Ca²⁺-activated kinase were found in the acinar cell extract. These substrate proteins were maximally phosphorylated in the combined presence of Ca²⁺ and phosphatidylserine. Calmodulin was partially effective as a cofactor for phosphorylation of the 38K substrate protein, but ineffective for the other three. A slight Ca²⁺/phospholipid-dependent phosphorylation of 38K and 30K proteins, but not of 22K and 15K proteins was seen in extract of isolated pancreatic islets. The K_a for Ca²⁺ for phosphorylation of the endogenous acinar cell proteins was decreased more than ten-fold in the combined presence of phosphatidylserine and unsaturated diacylglycerol. The presence of this Ca²⁺/phospholipid-dependent protein kinase/ protein phosphorylation system provides a potential mechanism of action for Ca²⁺ as a regulator of exocrine pancreatic function.