diacylglycerol

Diacylglycerol, or DAG, is the messenger that stays home. When phospholipase C cuts the membrane lipid in two, IP3 floats off into the interior, but DAG is greasy and remains embedded in the membrane, where it waits for its partner to arrive and gets to work right there.

DAG is the other product of phospholipase C acting on PIP2. Its main role is to activate protein kinase C: conventional protein kinase C isoforms need both DAG and the calcium that IP3 has just released, so the two messengers act as a coincidence detector — protein kinase C switches on fully only when both signals are present. Once active, protein kinase C phosphorylates target proteins to change cell behavior.

DAG's membrane location matters pharmacologically. Because phorbol esters mimic DAG and persistently activate protein kinase C, they are potent tumor promoters in the laboratory and a reminder that overdriving this pathway can favor cancer. Therapeutically, the more common approach is to block the upstream Gq-coupled receptor rather than DAG itself.