title: Phosphorylation of JNK is involved in regulation of H(+)-induced c-Jun expression.
abstract: Cells respond to physical and chemical stimulations mediated by pH, osmolarity, and oxidative and mechanical stresses. Various signal transduction pathways cooperate and participate in these responses. Here we describe the role of c-Jun NH2-terminal kinase (JNK) in regulation of gene transcription after an increase in extracellular H+. When cells were incubated in low pH medium, the promotion of JNK phosphorylation and c-Jun expression was clearly observed in cells in an extracellular pH- and time-dependent manner. Activation of p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) was extremely weak compared with that of JNK. An increase in extracellular H+ led to enhanced nuclear translocation of phosphorylated JNK leading to augmentation of the transcriptional activity of c-Jun. Nimodipine, a blocker of voltage-gated Ca2+ ion channels, prevented the phosphorylation of JNK and expression of c-Jun in a dose-dependent manner. These results suggest a novel intracellular signalling pathway for H+-induced c-Jun expression: an increase of extracellular H+ induces JNK phosphorylation and c-Jun expression via partly extracellular Ca2+ influx through voltage-gated Ca2+ channels.
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan. simokawa@med.gunma-u.ac.jp
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Qiu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Seki
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D010766:Phosphorylation; D011522:Protons; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D011522:Protons; D009553:Nimodipine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases