ERK5 MAP kinase regulates neurogenin1 during cortical neurogenesis

Autor: Chris Englund, Xin Duan, Junhui Zou, Guo Li Ming, Lidong Liu, Zhengui Xia, Yung Wei Pan, Glen M. Abel, Robert F. Hevner, Yupeng Wang, Paige Cundiff
Jazyk: angličtina
Rok vydání: 2009
Předmět:
MAPK/ERK pathway
Transcription
Genetic
MAP Kinase Signaling System
Neurogenesis
Recombinant Fusion Proteins
lcsh:Medicine
Nerve Tissue Proteins
Biology
Nestin
03 medical and health sciences
0302 clinical medicine
Intermediate Filament Proteins
Transcription (biology)
Basic Helix-Loop-Helix Transcription Factors
Animals
Humans
Phosphorylation
lcsh:Science
Molecular Biology
Transcription factor
Cells
Cultured
Mitogen-Activated Protein Kinase 7
030304 developmental biology
Neurons
Regulation of gene expression
0303 health sciences
Multidisciplinary
Kinase
Stem Cells
lcsh:R
Gene Expression Regulation
Developmental
Cell Biology
Rats
Cell biology
Enzyme Activation
Mitogen-activated protein kinase
biology.protein
lcsh:Q
030217 neurology & neurosurgery
Research Article
Developmental Biology
Neuroscience
Zdroj: PLoS ONE, Vol 4, Iss 4, p e5204 (2009)
PLoS ONE
ISSN: 1932-6203
Popis: The commitment of multi-potent cortical progenitors to a neuronal fate depends on the transient induction of the basic-helix-loop-helix (bHLH) family of transcription factors including Neurogenin 1 (Neurog1). Previous studies have focused on mechanisms that control the expression of these proteins while little is known about whether their pro-neural activities can be regulated by kinase signaling pathways. Using primary cultures and ex vivo slice cultures, here we report that both the transcriptional and pro-neural activities of Neurog1 are regulated by extracellular signal-regulated kinase (ERK) 5 signaling in cortical progenitors. Activation of ERK5 potentiated, while blocking ERK5 inhibited Neurog1-induced neurogenesis. Furthermore, endogenous ERK5 activity was required for Neurog1-initiated transcription. Interestingly, ERK5 activation was sufficient to induce Neurog1 phosphorylation and ERK5 directly phosphorylated Neurog1 in vitro. We identified S179/S208 as putative ERK5 phosphorylation sites in Neurog1. Mutations of S179/S208 to alanines inhibited the transcriptional and pro-neural activities of Neurog1. Our data identify ERK5 phosphorylation of Neurog1 as a novel mechanism regulating neuronal fate commitment of cortical progenitors.
Databáze: OpenAIRE
Externí odkaz: