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Titolo:
p38 mitogen-activated protein kinase-dependent activation of protein phosphatases 1 and 2A inhibits MEK1 and MEK2 activity and collagenase 1 (MMP-1) gene expression
Autore:
Westermarck, J; Li, SP; Kallunki, T; Han, JH; Kahari, VM;
Indirizzi:
Univ Turku, Ctr Biotechnol, FIN-20520 Turku, Finland Univ Turku Turku Finland FIN-20520 Biotechnol, FIN-20520 Turku, Finland Abo Akad Univ, FIN-20520 Turku, Finland Abo Akad Univ Turku Finland FIN-20520 kad Univ, FIN-20520 Turku, Finland Univ Turku, Dept Med Biochem & Dermatol, FIN-20520 Turku, Finland Univ Turku Turku Finland FIN-20520 & Dermatol, FIN-20520 Turku, Finland Danish Canc Soc, Inst Canc Biol, Apoptosis Lab, DK-2100 Copenhagen, Denmark Danish Canc Soc Copenhagen Denmark DK-2100 , DK-2100 Copenhagen, Denmark Scripps Clin & Res Inst, Dept Immunol, La Jolla, CA 92121 USA Scripps Clin& Res Inst La Jolla CA USA 92121 nol, La Jolla, CA 92121 USA
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 7, volume: 21, anno: 2001,
pagine: 2373 - 2383
SICI:
0270-7306(200104)21:7<2373:PMPKAO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHORBOL 12-MYRISTATE 13-ACETATE; N-TERMINAL KINASE; MAP KINASE; MATRIX METALLOPROTEINASE-1; OKADAIC ACID; SIGNAL-TRANSDUCTION; FIBROBLAST COLLAGENASE; TUMOR-SUPPRESSOR; AP-1 ACTIVITY; APOPTOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Westermarck, J Univ Turku, Ctr Biotechnol, Tykistokatu 6B, FIN-20520 Turku, Finland Univ Turku Tykistokatu 6B Turku Finland FIN-20520 Finland
Citazione:
J. Westermarck et al., "p38 mitogen-activated protein kinase-dependent activation of protein phosphatases 1 and 2A inhibits MEK1 and MEK2 activity and collagenase 1 (MMP-1) gene expression", MOL CELL B, 21(7), 2001, pp. 2373-2383

Abstract

Degradation of collagenous extracellular matrix by collagenase 1 (also known as matrix metalloproteinase 1 [MMP-1]) plays a role in the pathogenesis of various destructive disorders, such as rheumatoid arthritis, chronic ulcers, and tumor invasion and metastasis. Here, we have investigated the roleof distinct mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-1 gene expression. The activation of the extracellular signal-regulated kinase 1 (ERK1)/ERK2 (designated ERK1,2) pathway by oncogenic Ras,constitutively active Raf-1, or phorbol ester resulted in potent stimulation of MMP-1 promoter activity and mRNA expression. In contrast, activation of stress-activated c-Jun N-terminal kinase and p38 pathways by expression of constitutively active mutants of Rac, transforming growth factor beta -activated kinase 1 (TAK1), MAPK kinase 3 (MKK3), or MKK6 or by treatment with arsenite or anisomycin did not alone markedly enhance MMP-1 promoter activity. Constitutively active MKK6 augmented Raf-1-mediated activation of theMMP-1 promoter, whereas active mutants of TAK1 and MKK3b potently inhibited the stimulatory effect of Raf-1. Activation of p38 MAPK by arsenite also potently abrogated stimulation of MMP-1 gene expression by constitutively active Pas and Raf-1 and by phorbol ester. Specific activation of p38 alpha by adenovirus-delivered constitutively active MKK3b resulted in potent inhibition of the activity of ERK1,2 and its upstream activator MEK1,2. Furthermore, arsenite prevented phorbol ester-induced phosphorylation of ERK1,2 kinase-MEK1,2, and this effect was dependent on p38-mediated activation of protein phosphatase 1 (PP1) and PP2A, These results provide evidence that activation of signaling cascade MKK3-MKK3b-->p38 alpha blocks the ERK1,2 pathway at the level of MEK1,2 via PP1-PP2A and inhibits the activation of MMP-1gene expression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 13:49:50