title: VEGF upregulates Homer 1a gene expression via the mitogen-activated protein kinase cascade in cultured cortex neurons.
abstract: In alternative splice variants of Homer 1 transcripts, Homer 1a messenger RNA (mRNA) has been shown to be upregulated selectively and rapidly by neural stimulation and represents a member of the immediate early gene (IEG) family. In our study, Homer 1 variants were expressed in cultured neurons as investigated by RT-PCR and Western blot analysis. After stimulation of VEGF, neurons selectively upregulated Homer 1a mRNA via Flk-1. The induction of Homer 1a mRNA peaked at 2h and sustained to 8h, while no significant change was observed of Homer 1b/c mRNA levels. Inhibitor analysis as well as Western blot analysis has indicated that the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade plays an important role in VEGF-stimulated induction of Homer 1a mRNA. These results demonstrate that MAPK is a key mediator that links distinct extracellular VEGF stimuli to the transcriptional activation of Homer 1a mRNA.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Ma
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005786:Gene Expression Regulation; D000072233:Homer Scaffolding Proteins; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat