title: Multiple Gi proteins participate in nerve growth factor-induced activation of c-Jun N-terminal kinases in PC12 cells.
abstract: Nerve growth factor (NGF)-mediated activation of mitogen-activated protein kinases (MAPK) is critical for differentiation and apoptosis of PC12 cells. Since NGF employs stress-activated c-Jun N-terminal kinase (JNK) to regulate both programmed cell death and neurite outgrowth of PC12 cells, we examined NGF-regulated JNK activity and the role of G(i/o) proteins. Induction of JNK phosphorylation by NGF occurred in a time- and dose-dependent manner and was partially inhibited by pertussis toxin (PTX). To discern the participation of various signaling intermediates, PC12 cells were treated with specific inhibitors prior to NGF challenge. NGF-elevated JNK activity was abolished by inhibitors of JNK, p38 MAPK, Src, JAK3 and MEK1/2. NGF-dependent JNK phosphorylation became insensitive to PTX treatment upon transient expressions of Galpha(z) or the PTX-resistant mutants of Galpha(i1-3) and Galpha(oA). Collectively, these studies indicate that NGF-dependent JNK activity may be mediated via G(i1-3) proteins, JAK3, Src, p38 MAPK and the MEK/ERK cascade.
authors.affiliation: Department of Biochemistry, The Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Prudence H
authors.initials: PH
authors.lastname: Tso
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Morris
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Yung
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D004789:Enzyme Activation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D009154:Mutation; D020932:Nerve Growth Factor / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D020917:Receptor, trkA / Q000502:physiology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: C507936:Jak3 protein, rat; D020932:Nerve Growth Factor; D037342:Pertussis Toxin; D020917:Receptor, trkA; D053616:Janus Kinase 3; D019061:src-Family Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go