title: Leptin activates chicken growth hormone promoter without chicken STAT3 in vitro.
abstract: Leptin is an adipocyte-derived hormone that not only regulates food intake and energy homeostasis but also induces growth hormone (GH) mRNA expression and release, thereby controlling growth and metabolism in mammals. The molecular mechanism of leptin-induced regulation of GH gene transcription is unclear. The current study investigated the effects of leptin on the chicken GH (cGH) promoter and the molecular mechanism underlying leptin-induced cGH gene expression in vitro. Leptin activated the cGH promoter in the presence of chPit-1α in CHO cells stably expressing the chicken leptin receptor. Promoter activation did not require STAT-binding elements in the cGH promoter or STAT3 activity. However, JAK2 activation was required for leptin-dependent activity. JAK2-dependent pathways include p42/44 MAPK and PI3K, and inhibition of these pathways partially blocked leptin-induced cGH gene transcription. Although CK2 directly activates JAK2, a CK2 inhibitor blocked leptin-dependent activation of the cGH gene without affecting JAK2 phosphorylation. The CK2 inhibitor suppressed Erk1/2 and Akt phosphorylation. Additional data implicate Src family kinases in leptin-dependent cGH gene activation. These results suggest that leptin activates the cGH gene in the presence of chPit-1α via several leptin-activated kinases. Although further study is required, we suggest that the leptin-induced JAK2/p42/44 MAPK and JAK2/PI3K cascades are activated by Src-meditated CK2, leading to CBP phosphorylation and interaction with chPit-1α, resulting in transactivation of the cGH promoter.
authors.affiliation: College of Agriculture, Ibaraki University, 3-21-1 Chuo, Ami, Ibaraki 300-0393, Japan; United Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-81-1 Harumi, Fuchu, Tokyo 790-8566, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Murase
authors.affiliation: College of Agriculture, Ibaraki University, 3-21-1 Chuo, Ami, Ibaraki 300-0393, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Namekawa
authors.affiliation: College of Agriculture, Ibaraki University, 3-21-1 Chuo, Ami, Ibaraki 300-0393, Japan; United Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-81-1 Harumi, Fuchu, Tokyo 790-8566, Japan. Electronic address: takeshi.ohkubo.0533@vc.ibaraki.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohkubo
mesh_terms: D000818:Animals; D016466:CHO Cells; D002645:Chickens; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects; D013006:Growth Hormone / Q000235:genetics*; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054411:Receptors, Leptin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D020738:Leptin; D047428:Protein Kinase Inhibitors; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D013006:Growth Hormone; D053614:Janus Kinase 2; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: CK2; Growth hormone; JAK2; Leptin; Pit-1α