title: c-Jun N-terminal kinase regulates CTP:phosphocholine cytidylyltransferase.
abstract: CTP:phosphocholine cytidylyltransferase (CCTalpha) is a rate-regulatory enzyme required for phosphatidylcholine (PtdCho) synthesis. CCTalpha is also a phosphoenzyme, but the physiologic role of kinases on enzyme function remains unclear. We report high-level expression of two major isoforms of the c-Jun N-terminal kinase family (JNK1 and JNK2) in murine lung epithelia. Further, JNK1 and JNK2 phosphorylated purified CCTalpha in vitro, and this was associated with a dose-dependent decrease (approximately 40%) in CCT activity. To evaluate JNK in vivo, lung epithelial cells were infected with a replication defective adenoviral vector encoding murine JNK2 (Adv-JNK2) or an empty vector. Adv-JNK2 infection, unlike the empty vector, markedly increased JNK2 expression concomitant with increased incorporation of [32P]orthophosphate into endogenous CCTalpha. Although Adv-JNK2 infection only modestly reduced CCT activity, it reduced PtdCho synthesis by approximately 30% in cells. These observations suggest a role for JNK kinases as negative regulators of phospholipid synthesis in murine lung epithelia.
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. alan-ryan@uiowa.edu
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Ryan
authors.forename: Matthew
authors.initials: M
authors.lastname: Andrews
authors.forename: Jiming
authors.initials: J
authors.lastname: Zhou
authors.forename: Rama K
authors.initials: RK
authors.lastname: Mallampalli
mesh_terms: D000818:Animals; D002460:Cell Line; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism*; D003067:Coenzymes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000201:enzymology*
chemical_list: D003067:Coenzymes; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D019916:Choline-Phosphate Cytidylyltransferase