Tyrosine phosphorylation of protein kinase C.

Abstract

AbstractProtein kinase C (PKC) comprises a family of 10 isoforms divided into conventional, novel, and atypical groups according to the structural differences in their regulatory domains. The PKC isoforms are phosphorylated in the activation loop at a threonine residue conserved among the family. In addition, conventional and novel isoforms are phosphorylated at the two serine and/or threonine motif sites in the carboxyl-terminal end region, whereas atypical isoforms have a single threonine phosphorylation site in the carboxyl-terminal sequence (1,2). Phosphorylation on these threonine and serine residues is important to render the enzyme catalytically active. Recently, most of PKC isoforms have been revealed to be phosphorylated on tyrosine in vivo (3–9). Especially, the δ isoform of the novel group is phosphorylated on different tyrosine residues presumably by distinct stimuli, and the covalent modification reaction regulates its catalytic activity (10–14). The tyrosine phosphorylation sites are also identified for the θ isoform of the novel group (15) and the λ isoform of the atypical group (16). In contrast to serine and threonine phosphorylation, most of these tyrosine residues thus far detected are not conserved among the PKC family, suggesting that the tyrosine phosphorylation regulates the enzyme by a mechanism specific to each isoform rather than a common way for the whole family. Therefore, it is important to determine the tyrosine phosphorylation sites of each isoform induced by different stimuli to elucidate the control mechanism of the PKC family.KeywordsPhosphorylation SiteTyrosine PhosphorylationMass Spectrometric AnalysisTyrosine Phosphorylation SiteAtypical GroupThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.