Rottlerin is a Specific PKC Inhibitor

Protein kinase C (PKC) is a family of protein kinase enzymes with 15 isoforms that can regulate the protein function. PKCs can control the function of otherproteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. Therefore, PKCs plays an important in receptor desensitization, in modulating membrane structure events, in regulating transcription, in mediating immune responses, in regulating cell growth, and in learning and memory. 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.

PKCs have four structurally and functionally distinct subgroups: conventional, novel, atypical and the PKC-related kinases. The classical isoforms (cPKC) comprise PKCα, βI, βII, and γ. These require Ca2+, DAG, and a phospholipid such as phosphatidylserine for activation. The novel isoforms (nPKC), which include PKCδ, ε, η, and θ, requiring diacylglycerol and phospholipids, but they do not respond directly to Ca2+. The atypical isoforms (aPKC) include PKCι and PKCζ, do not depend on Ca2+ or diacylglycerol for activation, but are instead allosterically activated.

Rottlerin is a potent and specific PKC inhibitor.

Rottlerin, a polyphenol natural product, can be found in Mallotus Philippinensis. Importantly, Rottlerin is a specific and reversible PKC inhibitor. Importantly, Rottlerin can inhibit isoforms, including PKCα, β, γ, δ, ε, η and ζ. Rottlerin also inhibit CaM kinase III. Rottlerin acts as a direct uncoupler of mitochondrial oxidative phosphorylation. Besides, Rottlerin stimulates autophagy by targeting a signaling cascade upstream of mTORC1. Rottlerin induces apoptosis via caspase 3 activation. What’s more, Rottlerin inhibits HIV-1 integration and Rabies virus (RABV) infection.

All in all, Rottlerin is a potent, specific and reversible PKC inhibitor.

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