protein kinase C

Protein kinase C is the executive of the calcium branch of signaling, the counterpart of protein kinase A on the cyclic-AMP side. Where protein kinase A reads the cyclic-AMP signal, protein kinase C reads the DAG-and-calcium signal generated by the Gq/phospholipase C pathway.

Conventional protein kinase C isoforms require two things to switch on: diacylglycerol (DAG) in the membrane and a rise in intracellular calcium. When both appear, protein kinase C moves to the membrane, becomes active, and phosphorylates serine/threonine residues on a wide range of substrates — ion channels, contractile proteins, transcription factors, and other signaling proteins. There is a whole family of isoforms with somewhat different cofactor needs and tissue distributions.

Protein kinase C activity influences vascular tone, secretion, immune-cell function, and cell growth. Persistent activation is implicated in cancer and in the vascular complications of diabetes, which is why protein kinase C inhibitors have been explored as drugs (for example, ruboxistaurin for diabetic retinopathy). Conversely, phorbol esters that overactivate it are classic tumor promoters, underscoring how much depends on keeping this kinase appropriately controlled.