RGD Reference Report - ATF-1 mediates protease-activated receptor-1 but not receptor tyrosine kinase-induced DNA synthesis in vascular smooth muscle cells.PG - - Rat Genome Database

RGD Reference Report - ATF-1 mediates protease-activated receptor-1 but not receptor tyrosine kinase-induced DNA synthesis in vascular smooth muscle cells.PG - - Rat Genome Database

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ATF-1 mediates protease-activated receptor-1 but not receptor tyrosine kinase-induced DNA synthesis in vascular smooth muscle cells.PG -
Authors:	Ghosh, SK Gadiparthi, L Zeng, ZZ Bhanoori, M Tellez, C Bar-Eli, M Rao, GN
Citation:	Ghosh SK, etal., J Biol Chem 2002 Jun 14;277(24):21325-31.
RGD ID:	625519
Pubmed:	PMID:11925444 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M201608200 (Journal Full-text)
Previously we have demonstrated that activation of p38 mitogen-activated protein kinase (MAPK) and induction of DNA synthesis in response to receptor tyrosine kinase (RTK) and G protein-coupled receptor (GPCR) agonists require NADH/NADPH-like oxidase activity in vascular smooth muscle cells (VSMC). Here we tested the role of p38 MAPK in RTK and GPCR agonist-induced DNA synthesis in VSMC. Platelet-derived growth factor (PDGF)-BB and thrombin (RTK and GPCR agonists, respectively) activated p38 MAPK in a time-dependent manner in VSMC. Inhibition of p38 MAPK led to a 50% decrease in the DNA synthesis induced by thrombin but not PDGF-BB. ATF-1 was found to be the predominant member of the cyclic AMP response element (CRE)-DNA complex formed in VSMC in response to PDGF-BB and thrombin, and both agonists induced its phosphorylation. Regardless of this, inhibition of p38 MAPK reduced only thrombin- but not PDGF-BB-induced ATF-1 phosphorylation. Similarly, inhibition of p38 MAPK caused a 50% decrease in thrombin- but not PDGF-BB-induced CRE promoter-dependent transcription. Ectopic expression of an inhibitory anti-ATF-1 single-chain antibody fragment, ScFv, significantly interfered with DNA synthesis induced by thrombin but not PDGF-BB. Together, these results suggest the following conclusions. 1) Both RTK and GPCR agonists activate p38 MAPK and induce CRE promoter-dependent transcription; 2) both RTK and GPCR agonists induce ATF-1 phosphorylation, and ATF-1 is a predominant member in the CRE-DNA complexes formed in response to these agents; and 3) p38 MAPK-dependent ATF-1 phosphorylation and CRE promoter-mediated transcription are associated with GPCR agonist-induced VSMC growth.AD - Department of Physiology, University of Tennessee HealthScience Center, Memphis, Tennessee 38163, USA.FAU - Ghosh, Salil K

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of DNA replication		IMP		625519		RGD

Objects Annotated

Genes (Rattus norvegicus)

Atf1 (activating transcription factor 1)

Objects referenced in this article

Gene	Mapk14	mitogen activated protein kinase 14	Rattus norvegicus

Additional Information