Leptin-induced transactivation of NPY gene promoter mediated by JAK1, JAK2 and STAT3 in the neural cell lines.
Neuropeptide Y (NPY) plays an important role in the central and sympathetic regulation of food intake and blood pressure. Although the NPY gene expression is regulated by a number of agents such as leptin, the mechanism responsible for leptin-induced regulation of the transcription of the NPY gene remains to be explored. In this study, the NPY gene promoter was transactivated by leptin in N18TG2, NG108-15 and PC12 cells which expressed the functional leptin receptor. The long isoform of leptin receptor (OB-Rb) could induce the transactivation, but the C-terminal truncated form (OB-Ra) could not. When dominant negative type of STAT3, JAK1 or JAK2 and was co-expressed, the leptin-induced transactivation was suppressed almost completely. The leptin-response element which confers NPY gene transactivation by leptin was determined in the 221-bp region of rat NPY gene promoter (-553/-335), where two STAT3-binding site-like elements (TCCAGTA) exist. These results indicated that activation of JAK1, JAK2 and STAT3 is necessary for leptin-induced transactivation of NPY gene through the leptin-response element in these neural cells.
Muraoka
Osamu
O
Division of Pharmacology, Department of Molecular Genetics, Course for Molecular and Cellular Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951 8510, Japan.
Xu
Bo
B
Tsurumaki
Tatsuru
T
Akira
Shizuo
S
Yamaguchi
Tsuyoshi
T
Higuchi
Hiroshi
H
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology; D004594:Electrophysiology; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051381:Rats; D020218:Response Elements / Q000502:physiology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D020738:Leptin; D009478:Neuropeptide Y; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507905:Jak1 protein, mouse; C507906:Jak1 protein, rat; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2