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Protein kinase C (PKC) was first isolated from the brain by Yasutomi Nishizuka and his colleagues in 1977. It was obtained as a proenzyme that was switched on during proteolysis forming a serine and or threonine-protein kinase activity which is referred to as protein kinase M (PKM). The kinase activity of this enzyme has several functions. Enzyme interest was brought about by discovering that free calcium ions (Ca2+) and membrane phospholipids could together activate PKC even in the absence of proteolysis. This was done by Kishimoto in 1980.
Most Protein Kinase C function opinions are based on PKC activation assays based on the amount of membrane-bound Ca2+ and or phospholipids dependent kinase activity.
There are at least 10 members of the PKC family, which is classified into three subgroups: classical PKCs (alpha, betaI, betaII, gamma), new PKCs (delta, epsilon, eta, theta), and atypical PKCs (zeta, iota/lambda). The unique cofactor needs, tissue distribution, and cellular compartmentalization imply that each isoform has diverse roles and fine-tuned signaling cascades.
PKC is a family within cyclic AMP regulated kinases and cyclic GMP regulated kinases. They phosphorylate their substrate at specific sites which contain serine and threonine residues. PKCs are associated with two N-terminal domains C1 and C2 domains. C1 domain is sensitive towards phospholipids like diacylglycerols (DAGs). C2 domains are sensitive towards Ca2+. Some PKCs only have the C1 domains. But both types of PKCs are downstream effectors of the phospholipase C coupled receptors. PKC is also comprised of several isoforms like alpha, beta l and beta ll. Some of these isoforms regulate integrin affinity for extra cellular matrix (ECM) ligands. Integrins attach adhesion molecules like P- selectins upregulated during inflammation. Integrins are found on the surface of leukocytes.
Binding of integrins to the adhesion molecules like P- selectins allows for movement of leukocytes through the endothelium, a process called diapedesis. Outside in signaling of integrins can activate PKC isoforms leading to regulation of cell migration. For instance, a phospholipid product called p13k metabolites activates PKC regulating cell migration.
PKC that does not depend on Ca2+ or phospholipids for activation can also be found, it is this called a cognitive kinase.
After temporary activation dependent of say Ca2+ and independent PKC, some continue to remain active and are sovereign from Ca2+ and phospholipids. They stop cell migration by destroying receptors that contain serine and threonine residues.
PKC cause contraction of smooth muscles. They do so by phosphorylating an action binding protein called calponin. This reverses the inhibition of actin- activated myosin ATPase. This allows actin to interact with myosin thus increasing contraction of smooth muscles like vascular smooth muscles (VSM).