PKCη is a member of a new PKC isoenzyme that regulates cell proliferation, differentiation, secretion and apoptosis. It is mainly expressed in epithelial cells and has the highest homology to PKCε. PKCη is up-regulated in breast cancer tissues, and overexpression of PKCη is related to drug resistance to chemotherapy drugs. Although PKCs are involved in tumor development, PKCη is the only PKC isoenzyme that is sensitive to phorbol ester, and its resistance is down-regulated after long-term treatment with phorbol ester. Little is known about the unique regulation of PKCη. In contrast to traditional and new PKCs that are down-regulated after continuous treatment with PKC activators, PKCη is up-regulated in response to PKC activators and down-regulated after treatment with PKC inhibitors.

Figure 1. Protein structure of PKCη.

Introductions

Protein kinase C is a family of phospholipid-dependent serine / threonine kinases and plays a key role in signal transduction and cellular regulation. According to their structural characteristics, the PKC family can be divided into three categories: conventional (α, βI, βII, and γ), new (δ, ε, η, θ), and atypical (ζ, λ / ι). Although traditional PKC requires Ca²⁺ and diacylglycerol (DAG) to function, the new PKC is not sensitive to Ca²⁺, but it is related to DAG, while non-typical PKC is not sensitive to both Ca²⁺ and DAG. PKC isoenzymes differ in biochemical properties, tissue-specific distribution, and intracellular localization. Most cells express multiple PKC isoenzymes, which display overlapping and unique functions. PKCs are not only regulated by cofactors but also phosphorylated. PKCs are phosphorylated at conserved residues in the activation loop, turning motif and hydrophobic motif. Phosphorylation of PKC activates them and regulates their stability and subcellular localization. PKC is regulated by autophosphorylation and transphosphorylation. It is generally believed that PKC-induced phosphorylation occurs on the activation loop of phosphoinositide-dependent kinase-1 (PDK1), followed by autophosphorylation at turns and on hydrophobic motifs. However, recent research suggests that PKC may also be transphosphorylated by other members of the PKC family. For example, PKCδ has been shown to be transphosphorylated by PKCε and vice versa. This cross-regulation of PKC may be an important way to integrate signals through various PKC isoenzymes. PKCη is a member of a new PKC isoenzyme that regulates cell proliferation, differentiation, secretion and apoptosis. It is mainly expressed in epithelial cells and has the highest homology to PKCε. PKCη is up-regulated in breast cancer tissues, and overexpression of PKCη is associated with resistance to chemotherapy drugs.

References

1. Micol V; et al. Correlation between protein kinase C alpha activity and membrane phase behavior. Biophysical Journal. 1999, 76 (2): 916-7.
2. Steinberg SF; et al. Distinctive activation mechanisms and functions for protein kinase Cdeha. Bioehem J, 2004, 384 (Pt 3): 449-459