down-regulation of Protein kinase C. Loss-of-function mutations and low PKC protein levels are prevalent in cancer, supporting a general tumor-suppressive role for Protein kinase C. Protein kinase C enzymes are important mediators of vascular permeability and have been implicated in various vascular diseases including disorders associated with hyperglycemia in diabetes mellitus, as well as endothelial injury and tissue damage related to cigarette smoke. Low-level PKC activation is sufficient to reverse cell chirality through phosphatidylinositol 3-kinase/AKT signaling and alters junctional protein organization between cells with opposite chirality, leading to an unexpected substantial change in endothelial permeability, which often leads to inflammation and disease. Inhibitors Protein kinase C inhibitors, such as ruboxistaurin, may potentially be beneficial in peripheral diabetic nephropathy. Chelerythrine is a natural selective PKC inhibitor. Other naturally occurring PKCIs are miyabenol C, myricitrin, gossypol. Other PKCIs : Verbascoside, BIM-1, Ro31-8220. Bryostatin 1 can act as a PKC inhibitor; It was investigated for cancer. Tamoxifen is a PKC inhibitor. Activators The Protein kinase C activator ingenol mebutate, derived from the plant Euphorbia peplus, is FDA-approved for the treatment of actinic keratosis. Bryostatin 1 can act as a PKCe activator and as of 2016 is being investigated for Alzheimer's disease. 12-O-Tetradecanoylphorbol-13-acetate (PMA or TPA) is a diacylglycerol mimic that can activate the classical PKCs. It is often used together with ionomycin which provides the calcium-dependent signals needed for activation of some PKCs. See also Serine/threonine-specific protein kinase Signal transduction Yasutomi Nishizuka, discovered protein kinase C Ccdc60 References External links EC 2.7.11 Protein kinases