PKC (Protein kinase C) is a family of protein kinase enzymes. In mammals, the PKC family members has four structurally and functionally distinct subgroups according to their regulatory domains. These are the classical isoforms (cPKC), novel isoforms (nPKC), atypical isoforms (aPKC) and the PKC-related kinases (PKN). PKC can control the function of otherproteins through the phosphorylation these proteins, such as receptor desensitization, in modulating membrane structure events, in regulating transcription, in mediating immune responses, in regulating cell growth, and in learning and memory.

Interestingly, PKCs in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca²⁺). Hence PKCs play important roles in several signal transduction cascades. cPKCs comprise PKCα, βI, βII, and γ. These require Ca²⁺, DAG, and a phospholipid such as phosphatidylserine for activation. The nPKCs, which include PKCδ, ε, η, and θ, requiring diacylglycerol and phospholipids, but they do not respond directly to Ca²⁺. The aPKCs, which include PKCι and PKCζ, do not depend on Ca²⁺ or diacylglycerol for activation, but are instead allosterically activated.

Ro 31-8220, a potent PKC inhibitor, can inhibit PKCα, PKCβI, PKCβII, PKCγ and PKCε. Ro 31-8220 also inhibits wide range of kinases inlcuding MAPKAP-K1b, MSK1, S6K1 and GSK3β. In rat adipocytes and L6 myotubes, Ro 31-8220 activates JNK and glycogen synthase, and inhibits MAPK and ERK2. Moreover, Ro 31-8220 directly suppresses voltage-dependent Na⁺ channels in the micromolar range. Besides, it can restore the TGF-β-induced tumor suppression activity in SMAD4 mutant cancer cells. Ro 31-8220 is neuroprotective against paraoxon-induced neuronal cell death in cerebellar granule neurons. What’s more, Ro 31-8220 has well tolerance, and has half-life of 5.7 hours in mice.

References:

[1] Rosse C, et, al. Nat Rev Mol Cell Biol. 2010 Feb;11(2):103-12.