Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways
Autore:
Davis, ME; Cai, H; Drummond, GR; Harrison, DG;
Indirizzi:
Emory Univ, Div Cardiol, WMB 319, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 v Cardiol, WMB 319, Atlanta, GA 30322 USA Emory Univ, Mol & Syst Pharmacol Program, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 Pharmacol Program, Atlanta, GA 30322 USA Atlanta Vet Hosp Med Ctr, Atlanta, GA USA Atlanta Vet Hosp Med Ctr Atlanta GA USA et Hosp Med Ctr, Atlanta, GA USA
Titolo Testata:
CIRCULATION RESEARCH
fascicolo: 11, volume: 89, anno: 2001,
pagine: 1073 - 1080
SICI:
0009-7330(20011123)89:11<1073:SSRENO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; RECEPTOR TYROSINE KINASES; POSTTRANSCRIPTIONAL REGULATION; INTRACELLULAR CALCIUM; CELLS TRANSDUCE; GENE-EXPRESSION; MESSENGER-RNA; PHOSPHORYLATION; MECHANOTRANSDUCTION; IDENTIFICATION;
Keywords:
endothelial nitric oxide synthase; c-Src; ERK1/2; Raf; mRNA stability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Harrison, DG Emory Univ, Div Cardiol, WMB 319, 1639 Pierce Dr, Atlanta, GA30322 USA Emory Univ 1639 Pierce Dr Atlanta GA USA 30322 , GA 30322 USA
Citazione:
M.E. Davis et al., "Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways", CIRCUL RES, 89(11), 2001, pp. 1073-1080

Abstract

In this study, we defined the signaling cascade responsible for increased eNOS mRNA expression in response to laminar shear stress. This pathway depends on the tyrosine kinase c-Src because shear induction of eNOS mRNA is blocked by the c-Src inhibitors PP1 and PP2, as well as an adenovirus encoding kinase inactive c-Src. After activation of c-Src, this pathway diverges. One arm is responsible for the short-term (6 hour) increase in eNOS mRNA. This involves a transient, 1-hour increase in eNOS transcription, as detected by nuclear run-on, that is dependent on activation of Ras and is blocked by adenoviral infection with dominant negative Ras. Downstream of Ras, MEK1/2 and ERK1/2 are important in this pathway, as 2 inhibitors of MEK1/2, PD98059 and UO126, completely prevented this early increase in eNOS mRNA. ERK1/2 was rapidly phosphorylated in response to shear, and this was prevented by c-Src and Ras inhibition. Further, Raf is phosphorylated in response to shear stress, and this is prevented by c-Src inhibition, suggesting that Raf may transduce the signal between Ras and ERK1/2. The second arm of the pathway linking activation of c-Src to eNOS expression involves stabilizationof eNOS mRNA by shear stress. This response to shear is completely abrogated by the c-Src inhibitor PP1 but not altered by Ras or MEK1/2 inhibition. Thus, c-Src plays a central role in modulation of eNOS expression in response to shear stress via divergent pathways involving a short-term increase in eNOS transcription and a longer-term stabilization of eNOS mRNA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 05:52:52