Nerve growth factor activates kinases that phosphorylate atypical protein kinase C.
Activation of atypical protein kinase C by nerve growth factor (NGF) involves phosphorylation. In order to identify kinases that regulate atypical PKC (aPKC), we surveyed PC12 cell lysates for protein kinases that are activated by NGF and which could phosphorylate aPKC. Employing an in-gel kinase assay where aPKC-zeta was copolymerized within the gel matrix as a substrate, three kinases, pp175, pp87 and pp60, were identified as enzymes that phosphorylated aPKC. Phosphorylation of aPKC by these three kinases coincided with NGF-induced activation of the enzyme. Each kinase possessed a unique subcellular distribution pattern and could be activated by either ceramide or H(2)0(2), second messengers that mimic NGF signaling events. Upstream, pp175 and pp60 lie in a ras pathway, whereas pp87 lies in a pathway dependent upon src. Altogether, these findings reveal that the aPKCs are subject to regulation by a novel group of kinases.
Vandenplas
Michel L
ML
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Mamidipudi
Vidya
V
Lamar Seibenhener
M
M
Wooten
Marie W
MW
D000818:Animals; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D018411:Spodoptera / Q000235:genetics; D013379:Substrate Specificity; D000099221:Protein Kinase C zeta
D002518:Ceramides; D006861:Hydrogen Peroxide; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D011494:Protein Kinases; D000099221:Protein Kinase C zeta; C115015:PKC-3 protein