PKCα: regulation and implication for cellular transformation

The protein kinase C (PKC) represents a family of closely related ser/thr protein kinase that participate in numerous signaling pathways. These signal control multiple cellular processes such as proliferation, differentiation, migration, apoptosis invasion and so on. Therefore, deregulation of PKC activity has been linked to numerous pathophysiological status, including cancer, Alzheimer, Parkinson disease, diabetes etc.1 Subsequently, based on the regulatory domain architecture, 10 different isoform of PKC can be divided into 3 subfamilies; the conventional PKC (cPKC: α, βI, βII and γ), novel PKC (nPKC: δ, θ, ε & ƞ) and atypical PKC (aPKC: ζ, λ/ɩ). PKC-α is a member of cPKC, containing 672 amino acid and ubiquitously expressed Ser/Thr protein kinase.2 Similar to other members of cPKC subfamily, PKC-α have the same architecture with a variable N-terminal regulatory moiety, and a highly conserved kinase domain at the C-terminal. The conserved catalytic domain contains a C3 (ATP binding) and a C4 (substrate binding) domain, and the regulatory domain comprises a C1 (DAG binding) and C2 (Ca2+ coordinating) domain and a pseudosubstrate sequence in Figure 1.