Activation of protein kinase C by tyrosine phosphorylation in response to H 2 O 2

• DOI: 10.1073/pnas.94.21.11233
• Publication Date: 2002-07-26T14:32:33Z
• Authors: Hiroaki Konishi; Motonari Tanaka; Yukitoshi Takemura; Hidenori Matsuzaki; Yoshitaka Ono; Ushio Kikkawa; Yasutomi Nishizuka
• Keywords: 0303 health sciences; Binding Sites; Molecular Sequence Data; Hydrogen Peroxide; Transfection; Peptide Mapping; Peptide Fragments; Recombinant Proteins; Enzyme Activation; Isoenzymes; 03 medical and health sciences; Amino Acid Substitution; COS Cells; Mutagenesis, Site-Directed; Animals; Tyrosine; Amino Acid Sequence; Phosphorylation; Sequence Alignment; Conserved Sequence; Protein Kinase C

Protein kinase C (PKC) isoforms, α, βI, and γ of cPKC subgroup, δ and ɛ of nPKC subgroup, and ζ of aPKC subgroup, were tyrosine phosphorylated in COS-7 cells in response to H 2 O 2 . These isoforms isolated from the H 2 O 2 -treated cells showed enhanced enzyme activity to various extents. The enzymes, PKC α and δ, recovered from the cells were independent of lipid cofactors for their catalytic activity. Analysis of mutated molecules of PKC δ showed that tyrosine residues, which are conserved in the catalytic domain of the PKC family, are critical for PKC activation induced by H 2 O 2 . These results suggest that PKC isoforms can be activated through tyrosine phosphorylation in a manner unrelated to receptor-coupled hydrolysis of inositol phospholipids.