Phosphatidylinositol-protein kinase C pathway

Schematic representation of the phosphatidylinositol pathway-protein kinase C pathway. The binding of a peptide hormone with its cell surface receptor (R) leads to activation of the associated stimulatory regulatory guanylyl protein (Gs) with a subsequent increase in activity of membrane-bound phospholipase C. This enzyme results in the breakdown of a membrane lipid, phosphatidylinositol 4,5-bisphosphate (PIP2), into two compounds: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mediates the immediate action of the hormone by inducing the release of calcium from stores in the smooth endoplasmic reticulum; and indirectly by enhancing the uptake of extracellular calcium ion. The increased intracellular calcium binds to calmodulin leading to the phosphorylation and activation of specific cell proteins and the physiologic effects of the hormone. Among the proteins phosphorylated and activated, with the cooperation of DAG, is calcium-dependent protein kinase C which initiates a further cascade of protein phosphorylation that mediates the sustained physiologic action of the hormone.