Comprehensive Technology Information

Protein Kinase C

Protein kinase C is an effector in the G protein-coupled receptor system. It is water-soluble in an inactive state, and is freely present in the cytosol. It becomes a membrane-bound enzyme after activation. The activation of protein kinase C is lipid-dependent and requires the presence of membrane lipid DAG, which is also Ca2+-dependent and requires an increase in the Ca2+ concentration in the cytosol. When DAG appears in the plasma membrane, protein kinase C in the cytosol is bound to the plasma membrane, and then activated by Ca2+. Like protein kinase A, protein kinase C belongs to multifunctional serine and threonine kinases.


All subclasses of PKC consist of a single peptide chain, with a molecular weight of approximately 67-83 kDa, and their structure can be divided into four conserved regions C1-C4 (mPKC and aPKC lack the C2 region) and five Variable zone V1-V5. The C1 region may be a membrane-bound region and contains a cysteine-rich random repeat Cys-X2-Cys-X13 (14) -Cys-X2-Cys-X7-Cys-X7-Cys (X represents An amino acid), this sequence is related to the cysteine-zinc-DNabinding finger conserved sequence Cys-X2- Cys-X13-Cys-X2-Cys is similar. Analysis of the peptide fragment of PKC revealed that the sequence is related to the binding of phorbol ester and diacylglycerol (DAG). The C2 region is related to the sensitivity of PKC to Ca2+. C1 and C2 are structurally different from other protein kinases and can bind Ca2+, phospholipids, DAG, and TPA. Therefore, C1 and C2 regions are also called regulatory regions. The C3 region includes an ATP-binding sequence Gly-X-Gly-X-X-Gly-Lys. This region has a high degree of homology with the ATP-binding sites of other protein kinases, also known as the catalytic region. The C4 region contains a substrate-binding region that is required for recognition of phosphorylated substrates. At least 11 subtypes have been found, and their structures are somewhat conservative and different, leading to their functional and regulatory diversity. Newly synthesized PKC generally needs to undergo the programmed phosphorylation process of Activation-loop (A-loop), Turn motif (TM) and hydrophobic motif (HM) in order to mature and obtain further Activated functions.


The activity of PKC depends on the presence of calcium ions and phospholipids, but only in the presence of diacylglycerol (DAG), an intermediate product of phospholipid metabolism, calcium ions at physiological concentrations work, because DAG can increase the affinity of PKC for substrate. Phosphatidylinositol-4,5-bisphosphate (PIP2) is hydrolyzed by phospholipase-C to generate DAG and IP3. IP3 promotes the release of intracellular calcium ions and acts synergistically with DAG in the activation of PKC. 12-o-tertradecanoylphordol-13-acetate (TPA; or phorbol-12-myristate-13-acetate, PMA) is a tumor-promoting agent, because its base structure is similar to DAG Simulate DAG at concentration, activate PKC, and increase PKC affinity to 10-7M. PKC is the receptor of TPA. When TPA is inserted into the cell membrane, it can directly activate PKC instead of DAG. When cells are treated with high doses of TPA, PKC in the target cells can be rapidly depleted, which in turn affects cell signaling. A variety of chemicals or antibiotics have an inhibitory effect on PKC activity. According to the different PKC target sites of inhibitors, inhibitors can be divided into two groups: one group is inhibitors that act on the catalytic region, and they can be conserved with protein kinases. Residues bind, so there is no obvious selectivity for PKC; the other group is inhibitors acting on the regulatory region, which can be combined with Ca2+, phospholipids and diacylglycerol/phorbol esters, and thus have higher selectivity.


Protein kinase C is a cytoplasmic enzyme. In unstimulated cells, PKC is mainly distributed in the cytoplasm in an inactive conformation. Once there is a second messenger, PKC will become a membrane-bound enzyme. It can activate enzymes in the cytoplasm and participate in the regulation of biochemical reactions. It can also act on transcription factors in the nucleus and participate in the regulation of gene expression. Versatile enzyme.

Control of glucose metabolism

In liver cells, protein kinase C and protein kinase A cooperate to phosphorylate glycogen synthase, inhibit glucose-polymerizing enzyme activity, and promote glycogen metabolism

cAMP-mediated promotion of glycogen decomposition and inhibition of glycogen synthesis are caused by the combination of glucagon receptors and β-adrenergic receptors with the corresponding hormones; and IP3, DAG, and Ca2+ -mediated promotion of glycogen degradation Glycogen synthesis is caused by alpha adrenergic receptors and adrenaline. cAMP activates protein kinase A, while IP3, DAG, and Ca2+ activate protein kinase C.

Control of cell differentiation

Myogenin is a transcription factor that plays a key role in muscle cell differentiation. In myoblasts, protein kinase C can phosphorylate myogenins, inhibit the ability of myogenins to bind to DNA, and thus prevent cells from differentiating into muscle fibers.

Involved in gene expression regulation

Protein kinase C can participate in the control of gene expression in at least two ways. One way is that protein kinase activates a phosphorylated cascade system that phosphorylates MAP protein kinase. Phosphorylated MAP protein kinase phosphorylates the gene regulatory protein Elk-1 and activates it. Activated Elk-1 binds to a short DNA sequence (called a serum response element, SRE) and then co-regulates gene expression with another factor (a serum response factor, SRF). Another approach is the phosphorylation of protein kinases and activation of the inhibitory protein Iκ-B, which releases the gene regulatory protein NF-κ-B and enters the nucleus to activate the transcription of specific genes.

Participation in long-term suppression (LTD)

Long-term cerebellar inhibition of LTD is due to PKC activation indirectly or directly causing phosphorylation of AMPA receptors, which converts AMPA receptors into a stable desensitized state or internalizes the receptors, resulting in LTD.


  1. Wilson CH; et al. Steatosis inhibits liver cell store-operated Ca2+ entry and reduces ER Ca²⁺ through a protein kinase C-dependent mechanism. The Biochemical Journal. 2015, 466 (2): 379-90.

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