Protein kinase C (PKC) is a key enzyme family in signal transduction pathways. PKCs are a heterogeneous group of serine/threonine protein kinases that share a common requirement for phospholipids for activity, but differ in their dependency on other activators (Ca²⁺ Diacylglycerols (DAG) and phorbal esters). Conventional PKCs (cPKCs) require Ca²⁺ and DAG, novel PKCs (nPKCs) require only DAGs and atypical PKCs (aPKCs) require neither. At present the mammalian PKC family consists of 12 different isotypes. Many nonmammalian PKCs have also been identified. The diversity of PKC isotypes may provide an explanation for the range of processes in which PKC has been implicated. PKC takes part in cellular responses to various agonists including hormones, neurotransmitters and some growth factors. PKC has been extensively linked to cellular cancerous states (both in cultured cells and in clinical samples) and also to non-cancer disease processes including psoriasis. Lipid signalling pathways play a crucial role in PKC activation.

The phosphoinositide cycle culminating in the production of inositol triphosphate and DAG by phospholipase C is the most studied mechanism of PKC activation. However, agonist stimulated hydrolysis of other phospholipids, particularly phosphatidylcholine, is also involved in prolonged PKC activation. Two functional domains are found in all PKC isotopes, a carboxy-terminal catalytic domain. In the absence of activating cofactors the regulatory domain inhibits the kinase activity of the catalytic domain. This regulation is mediated by a pseudosubstrate sequence which has a nonphosphorylatable alanine substituted for a serine/threonine residue.

Activation of the enzyme by Ca²⁺, phospholipid, DAG or phorbal esters reduce the affinity of the pseudosubstrate site/catalytic site interaction, freeing the catalytic site for substrate phosphorylation. In addition to cofactor dependence, substrate range and subcellular localization are important factors in controlling PKC activity.