Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Modulation of juxtamembrane cleavage ("shedding") of angiotensin-converting enzyme by stalk glycosylation: Evidence for an alternative shedding protease
Autore:
Schwager, SLU; Chubb, AJ; Scholle, RR; Brandt, WF; Mentele, R; Riordan, JF; Sturrock, ED; Ehlers, MRW;
Indirizzi:
Univ Cape Town, Sch Med, Dept Biochem Med, ZA-7925 Observatory, South Africa Univ Cape Town Observatory South Africa ZA-7925 bservatory, South Africa Univ Cape Town, Dept Biochem, ZA-7700 Rondebosch, South Africa Univ Cape Town Rondebosch South Africa ZA-7700 Rondebosch, South Africa Univ Munich, Klin Chem & Klin Biochem Abt, D-80336 Munich, Germany Univ Munich Munich Germany D-80336 Biochem Abt, D-80336 Munich, Germany Harvard Univ, Sch Med, Ctr Biochem & Biophys Sci & Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Biophys Sci & Med, Boston, MA 02115 USA
Titolo Testata:
BIOCHEMISTRY
fascicolo: 32, volume: 38, anno: 1999,
pagine: 10388 - 10397
SICI:
0006-2960(19990810)38:32<10388:MOJC(O>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR-ALPHA; O-LINKED GLYCOSYLATION; GROWTH-FACTOR RECEPTOR; AMYLOID PRECURSOR PROTEIN; DECAY-ACCELERATING FACTOR; CELL-SURFACE EXPRESSION; HAMSTER OVARY CELLS; TRANSFERRIN RECEPTOR; PROTEOLYTIC RELEASE; MOLECULAR-CLONING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Sturrock, ED Univ Cape Town, Sch Med, Dept Biochem Med, ZA-7925 Observatory, South Africa Univ Cape Town Observatory South Africa ZA-7925 outh Africa
Citazione:
S.L.U. Schwager et al., "Modulation of juxtamembrane cleavage ("shedding") of angiotensin-converting enzyme by stalk glycosylation: Evidence for an alternative shedding protease", BIOCHEM, 38(32), 1999, pp. 10388-10397

Abstract

The role of juxtamembrane stalk glycosylation in modulating stalk cleavageand shedding of membrane proteins remains unresolved, despite reports thatproteins expressed in glycosylation-deficient cells undergo accelerated proteolysis. We have constructed stalk glycosylation mutants of angiotensin-converting enzyme (ACE), a type I ectoprotein that is vigorously shed when expressed in Chinese hamster ovary cells. Surprisingly, stalk glycosylation did not significantly inhibit release. Introduction of an N-linked glycan directly adjacent to the native stalk cleavage site resulted in a 13-residue, proximal displacement of the cleavage site, from the Arg-626/Ser-627 to the Phe-640/Leu-641 bond. Substitution of the wildtype stalk with a Ser-/Thr-rich sequence known to be heavily O-glycosylated produced a mutant (ACE-JGL) in which this chimeric stalk was partially O-glycosylated; incomplete glycosylation may have been due to membrane proximity. Relative to levels of cell-associated ACE-JGL, rates of basal, unstimulated release of ACE-JGL were enhanced compared with wild-type ACE. ACE-JGL was cleaved at an Ala/Thr bond, 14 residues from the membrane. Notably, phorbol ester stimulation andTAPI (a peptide hydroxamate) inhibition of release-universal characteristics of regulated ectodomain shedding-were significantly blunted for ACE-JGL,as was a formerly undescribed transient stimulation of ACE release by 3,4-dichloroisocoumarin. These data indicate that (1) stalk glycosylation modulates but does not inhibit ectodomain shedding; and (2) a Ser-/Thr-rich, O-glycosylated stalk directs cleavage, at least in part, by an alternative shedding protease, which may resemble an activity recently described in TNF-alpha convertase null cells [Buxbaum, J. D., et al. (1998) J. Biol. Chem. 273, 27765-27767].

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 06:15:31