RGD Reference Report - Coordinate Notch3-hairy-related transcription factor pathway regulation in response to arterial injury. Mediator role of platelet-derived growth factor and ERK. - Rat Genome Database

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Coordinate Notch3-hairy-related transcription factor pathway regulation in response to arterial injury. Mediator role of platelet-derived growth factor and ERK.

Authors: Wang, W  Campos, AH  Prince, CZ  Mou, Y  Pollman, MJ 
Citation: Wang W, etal., J Biol Chem 2002 Jun 28;277(26):23165-71.
RGD ID: 625426
Pubmed: PMID:11971902   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M201409200   (Journal Full-text)

The Notch family of receptors and downstream effectors plays a critical role in cell fate determination during vascular ontogeny. Moreover, the human cerebral autosomal dominant artriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome of premature stroke and dementia is a heritable arteriopathy with alterations in vascular smooth muscle cells (VSMCs) resulting from mutations within Notch3. However, the expression and regulation of the Notch and hairy-related transcription factor (HRT) pathway in adult VSMCs in vitro and in vivo remain poorly characterized. The present study documents that the well-described modulation of VSMC fate in response to vascular injury and growth factor activation involves a coordinate regulation of the Notch and HRT pathways. Furthermore, platelet-derived growth factor promotes a similar coordinate down-regulation of the Notch receptors and HRT genes in cultured VSMCs via an ERK-dependent signaling pathway. Moreover, we established that HRT1 and HRT2 are direct downstream target genes of Notch3 signaling in VSMCs and determined that the activity of the nuclear protein RBP-Jk is essential for their regulation. These findings provide initial insight into the context- and cell type-dependent coordinate regulation of Notch3 and downstream HRT transcriptional pathway effector genes in VSMCs in vitro and in vivo that may have important implications for understanding the role of Notch signaling in human health and vascular disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Notch3Ratcellular response to platelet-derived growth factor stimulus  IEP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NOTCH3HumanNotch signaling pathway   ISONotch3 (Mus musculus) RGD 
Notch3RatNotch signaling pathway   ISONotch3 (Mus musculus) RGD 
Notch3MouseNotch signaling pathway   IMP  RGD 
testRatNotch signaling pathway   ISS  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Hey1  (hes-related family bHLH transcription factor with YRPW motif 1)
Hey2  (hes-related family bHLH transcription factor with YRPW motif 2)
Heyl  (hes-related family bHLH transcription factor with YRPW motif-like)
Notch1  (notch receptor 1)
Notch2  (notch receptor 2)
Notch3  (notch receptor 3)
test  (test1)

Genes (Mus musculus)
Hey1  (hairy/enhancer-of-split related with YRPW motif 1)
Hey2  (hairy/enhancer-of-split related with YRPW motif 2)
Heyl  (hairy/enhancer-of-split related with YRPW motif-like)
Notch1  (notch 1)
Notch2  (notch 2)
Notch3  (notch 3)

Genes (Homo sapiens)
HEY1  (hes related family bHLH transcription factor with YRPW motif 1)
HEY2  (hes related family bHLH transcription factor with YRPW motif 2)
HEYL  (hes related family bHLH transcription factor with YRPW motif like)
NOTCH1  (notch receptor 1)
NOTCH2  (notch receptor 2)
NOTCH3  (notch receptor 3)


Additional Information