title: Membrane translocation of novel protein kinase Cs is regulated by phosphorylation of the C2 domain.
abstract: Ca(2+)-independent or novel protein kinase Cs (nPKCs) contain an N-terminal C2 domain of unknown function. Removal of the C2 domain of the Aplysia nPKC Apl II allows activation of the enzyme at lower concentrations of phosphatidylserine, suggesting an inhibitory role for the C2 domain in enzyme activation. However, the mechanism for C2 domain-mediated inhibition is not known. Mapping of the autophosphorylation sites for protein kinase C (PKC) Apl II reveals four phosphopeptides in the regulatory domain of PKC Apl II, two of which are in the C2 domain at serine 2 and serine 36. Unlike most PKC autophosphorylation sites, these serines could be phosphorylated in trans. Interestingly, phosphorylation of serine 36 increased binding of the C2 domain to phosphatidylserine membranes in vitro. In cells, PKC Apl II phosphorylation at serine 36 was increased by PKC activators, and PKC phosphorylated at this position translocated more efficiently to membranes. Moreover, mutation of serine 36 to alanine significantly reduced membrane translocation of PKC Apl II. We suggest that translocation of nPKCs is regulated by phosphorylation of the C2 domain.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Pepio
authors.forename: W S
authors.initials: WS
authors.lastname: Sossin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003001:Cloning, Molecular; D017931:DNA Primers; D008969:Molecular Sequence Data; D016296:Mutagenesis; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C