RGD Reference Report - Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration. - Rat Genome Database

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Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration.

Authors: Hsu, SP  Chen, TH  Chou, YP  Chen, LC  Kuo, CT  Lee, TS  Lin, JJ  Chang, NC  Lee, WS 
Citation: Hsu SP, etal., Atherosclerosis. 2011 Jul;217(1):83-9. doi: 10.1016/j.atherosclerosis.2011.02.051. Epub 2011 Mar 10.
RGD ID: 7248703
Pubmed: PMID:21440892   (View Abstract at PubMed)
DOI: DOI:10.1016/j.atherosclerosis.2011.02.051   (Journal Full-text)

We previously showed that progesterone (P4) inhibits the proliferation of rat aortic smooth muscle cells (RASMC). Here, we further demonstrate that P4 at physiologic levels (5-500 nM) concentration-dependently inhibited migration of cultured RASMC. The effect is blocked by pretreatment with progesterone receptor (PR) antagonist, RU486. The P4-induced RASMC migration inhibition was through RhoA inactivation induced by cSrc-enhanced RhoA degradation. The P4-induced increases of phosphorylated Src (pSrc) and PR-pSrc complex in RASMC were observed mainly in the membrane fraction. Pre-treatment with a cSrc inhibitor (PP2) or cSrc antisense oligonucleotides prevented the P4-induced decreases of the protein levels of RhoA, phosphorylated FAK (p-FAK) and paxillin phosphorylaton and migration inhibition in RASMC. These findings expend our knowledge of the basis of P4's effect on vascular smooth muscle cell migration and highlight novel pathways of signaling transduction of P4 through PR-mediated nongenomic mechanisms.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytosol located_inIDA 7248703; 7248703; 7248703PMID:21440892BHF-UCL 
membrane located_inIDA 7248703; 7248703; 7248703PMID:21440892BHF-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
GTPase activity enablesIDA 7248703PMID:21440892BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Pgr  (progesterone receptor)
Rhoa  (ras homolog family member A)
Rhob  (ras homolog family member B)
Rhoc  (ras homolog family member C)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)


Additional Information