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Titolo:
MEKK-1, a component of the stress (stress-activated protein kinase c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells
Autore:
Brown, JD; DiChiara, MR; Anderson, KR; Gimbrone, MA; Topper, JN;
Indirizzi:
Stanfordtanford,ch Med, Falk Cardiovasc Res Ctr, Dept Med,Div Cardiovasc, S Stanford Univ Stanford CA USA 94305 c Res Ctr, Dept Med,Div Cardiovasc, S Harvardton,v, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Vasc Res, Bos Harvard Univ Boston MA USA 02115 mens Hosp, Dept Pathol,Div Vasc Res, Bos
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 13, volume: 274, anno: 1999,
pagine: 8797 - 8805
SICI:
0021-9258(19990326)274:13<8797:MACOTS>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; FLUID MECHANICAL STIMULI; VASCULAR ENDOTHELIUM; SIGNAL-TRANSDUCTION; SHEAR-STRESS; KAPPA-B; SMAD2; PHOSPHORYLATION; RECEPTOR; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Topper, JN Stanford00niv, Sch Med, Falk Cardiovasc Res Ctr, Dept Med,Div Cardiovasc, 3 Stanford Univ 300 Pasteur Dr Stanford CA USA 94305 ardiovasc, 3
Citazione:
J.D. Brown et al., "MEKK-1, a component of the stress (stress-activated protein kinase c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells", J BIOL CHEM, 274(13), 1999, pp. 8797-8805

Abstract

Smad proteins are essential components of the intracellular signaling pathways utilized by members of the transforming growth factor-beta (TGF-beta) superfamily of growth factors. Certain Smad proteins (e.g. Smad1, -2, and -3) can act as regulated transcriptional activators, a process that involvesphosphorylation of these proteins by activated TGF-beta superfamily receptors, We demonstrate that the intracellular kinase mitogen-activated proteinkinase kinase kinase-1 (MEKK-1), an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase pathway, can participate in Smad2-dependent transcriptional events in cultured endothelial cells, A constitutively active form of MEKK-1 but not mitogen-activated protein kinase kinase-1 (MEK-1) or TGF-beta-activated kinase-1, two distinct intracellular kinases, can specifically activate a Gal4-Smad2 fusion protein, and this effect correlates with an increase in the phosphorylation state of the Smad2 protein. These effects do not require the presence of the C-terminal SSXS motif of Smad2 that is the site of TGF-beta type 1 receptor-mediated phosphorylation. Activation of Smad2 by active MEKK-1 results in enhanced Smad2-Smad4 interactions, nuclear localization of Smad2 and Smad4, and the stimulation of Smad protein-transcriptional coactivator interactions in endothelial cells, Overexpression of Smad7 can inhibit the MEKK-1-mediated stimulation of Smad2 transcriptional activity, A physiological level of fluid shear stress, a known activator of endogenous MEKK-1 activity in endothelial cells, can stimulate Smad2-mediated transcriptional activity. These data demonstrate a novel mechanism for activation of Smad protein-mediated signaling in endothelial cells and suggest that Smad2 may act as an integrator of diverse stimuli in these cells.

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Documento generato il 28/09/20 alle ore 15:36:10