Molecules transmitting signals into cells often act through receptors in the plasma membrane that stimulate production of second messengers. When activated by a plasma membrane receptor, the enzyme phospholipase C (PLCg) hydrolyzes the membrane lipid phosphatidylinositol (PIP2) into the second messengers diacylglycerol (DAG) and IP3. IP3 releases calcium from intracellular stores into the cytoplasm where calcium alters many cellular activities, including activating protein kinase C. DAG also activates protein kinase C. Biologists often study signaling by artificially manipulating pathways using molecules like ionomycin and phorbol esters as research tools. Ionomycin is a molecule that carries calcium through the plasma membrane to increase the calcium concentration in the cytoplasm and activate protein kinase C without activating phospholipase C. Phorbol esters are molecules that mimic the action of DAG in the activation of protein kinase C, and were originally identified as tumor-promoting agents. The combination of ionomycin and phorbol esters is often used experimentally to study the effect of calcium and DAG signaling in cellular responses like T cell activation.

Ion Channel and Phorbal Esters Signaling Pathway References