Pulmonary hyperplasia and the two sides of PKC

Abstract

Protein kinase C (PKC) was initially identified by Nishizuka and coworkers1 as a nucleotide-independent, Ca2+-dependent serine kinase. Molecular cloning identified at least 11 isozymes of PKC that were further divided into subfamilies based on sequence homology and mode of stimulation. The classical PKCs (α, βI, βII, and γ) are diacylglycerol (DAG) and calcium-dependent enzymes, whereas the novel PKCs (δ, e, θ, and η) require DAG, but not calcium, for activation. The atypical PKCs (ζ, ι/λ) are not responsive to activation by DAG or calcium, but are activated by other lipid-derived second messengers. PKCs contain N-terminal regulatory and C-terminal catalytic domains separated by a flexible hinge region. In the absence of activating cofactors, the catalytic domain is subject to autoinhibition by the regulatory domain that is mediated, in part, by a pseudosubstrate sequence motif resembling the consensus sequence for phosphorylation by PKC.2 PKCs in general are involved in multiple intracellular … *Corresponding author. Tel: +49 30 4593 2413; fax: +49 30 4593 2415. E-mail address : graf{at}dhzb.de