title: Phosphorylation of ATF2 and interaction with NFY induces c-Jun in the gonadotrope.
abstract: Induction of c-Jun and c-Fos, partners that comprise the AP1 transcription factor, is critical for GnRH regulation of FSHβ gene expression. The signaling pathways that are necessary for regulation of AP1 in the gonadotrope cell are not known. Here, we investigate the mechanism of c-Jun induction by GnRH, the sole regulator of c-Jun in the gonadotrope. We identify that GnRH phosphorylates ATF2 via p38 and JNK, the same pathways responsible for GnRH induction of c-Jun. Upon phosphorylation, ATF2 binds the CRE element within the c-Jun proximal promoter and interacts with NFY. Functional ATF2 is necessary for both GnRH induction of c-Jun and FSHβ. Taken together, these studies elucidate the specificity of c-Jun induction by GnRH in the gonadotrope by demonstrating GnRH activation of the p38 and JNK signaling pathways that lead to phosphorylation of ATF2, providing critical insight into GnRH regulation of its target gene, the gonadotropin subunit FSHβ.
authors.affiliation: Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California San Diego, La Jolla, CA 92093-0674, USA. llindaman@ucsd.edu
authors.forename: Lacey L
authors.initials: LL
authors.lastname: Lindaman
authors.forename: Debra M
authors.initials: DM
authors.lastname: Yeh
authors.forename: Changchuan
authors.initials: C
authors.lastname: Xie
authors.forename: Kellie M
authors.initials: KM
authors.lastname: Breen
authors.forename: Djurdjica
authors.initials: D
authors.lastname: Coss
mesh_terms: D051697:Activating Transcription Factor 1 / Q000378:metabolism; D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D052681:Gonadotrophs / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D020935:MAP Kinase Signaling System; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051697:Activating Transcription Factor 1; D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; C497100:Atf1 protein, mouse; C497106:Atf2 protein, mouse; C103002:Atf3 protein, mouse; D023081:CCAAT-Binding Factor; D016755:Proto-Oncogene Proteins c-jun; C402244:nuclear factor Y; D007987:Gonadotropin-Releasing Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases