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Titolo:
Stimulation-induced down-regulation of tumor necrosis factor-alpha converting enzyme
Autore:
Doedens, JR; Black, RA;
Indirizzi:
Immunex Corp, Dept Res Adm, Seattle, WA 98101 USA Immunex Corp Seattle WAUSA 98101 rp, Dept Res Adm, Seattle, WA 98101 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 19, volume: 275, anno: 2000,
pagine: 14598 - 14607
SICI:
0021-9258(20000512)275:19<14598:SDOTNF>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; L-SELECTIN; TNF RECEPTOR; GROWTH-FACTOR; METALLOPROTEASE-DISINTEGRIN; STRUCTURAL REQUIREMENTS; SECRETASE CLEAVAGE; BINDING-PROTEIN; T-LYMPHOCYTES; IL-6 RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Doedens, JR Immunex Corp, Dept Res Adm, 51 Univ St, Seattle, WA 98101 USA Immunex Corp 51 Univ St Seattle WA USA 98101 tle, WA 98101 USA
Citazione:
J.R. Doedens e R.A. Black, "Stimulation-induced down-regulation of tumor necrosis factor-alpha converting enzyme", J BIOL CHEM, 275(19), 2000, pp. 14598-14607

Abstract

The extracellular domains of many proteins, including growth factors, cytokines, receptors, and adhesion molecules, are proteolytically released fromcells, a process termed "shedding. " Tumor necrosis factor-alpha convertingenzyme (TACE/ADAM-17) is a metalloprotease-disintegrin that sheds tumor necrosis factor-alpha and other proteins. To study the regulation of TACE-mediated shedding, we examined the effects of stimulation of cells on TACE localization and expression. Immunofluorescence microscopy revealed a punctatedistribution of TACE on the surface of untreated cells, and stimulation ofmonocytic cells with lipopolysaccharide did not affect TACE staining. Phorbol 12-myristate 13-acetate (PMA), a potent inducer of shedding, decreased cell-surface staining for TACE. Surface biotinylation experiments confirmedand extended this observation; PMA decreased the half-life of surface-biotinylated TACE without increasing the turnover of total cell-surface proteins. Soluble fragments of TACE were not detected in the medium of cells that had down-regulated TACE, and TACE was not down-regulated when endocytosis was inhibited. Antibody uptake experiments suggested that cell-surface TACE was internalized in response to PMA. Surprisingly, a metalloprotease inhibitor prevented the PMA-induced turnover of TACE. Thus, PIMA activates shedding and causes the down-regulation of a major "sheddase," suggesting that induced shedding may be regulated by a mechanism that decreases the amount ofactive TACE on the cell surface.

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Documento generato il 05/04/20 alle ore 18:59:49