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Titolo:
Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites
Autore:
Woodman, ZL; Oppong, SY; Cook, S; Hooper, NM; Schwager, SLU; Brandt, WF; Ehlers, MRW; Sturrock, ED;
Indirizzi:
Univ Cape Town, Dept Med Biochem, ZA-7700 Rondebosch, South Africa Univ Cape Town Rondebosch South Africa ZA-7700 Rondebosch, South Africa Univ Leeds, Sch Biochem & Mol Biol, Leeds LS2 9JT, W Yorkshire, England Univ Leeds Leeds W Yorkshire England LS2 9JT S2 9JT, W Yorkshire, England Univ Cape Town, Dept Biochem, ZA-7700 Rondebosch, South Africa Univ Cape Town Rondebosch South Africa ZA-7700 Rondebosch, South Africa Univ Cape Town, MRC, Liver Res Ctr, ZA-7925 Cape Town, South Africa Univ Cape Town Cape Town South Africa ZA-7925 25 Cape Town, South Africa
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 347, anno: 2000,
parte:, 3
pagine: 711 - 718
SICI:
0264-6021(20000501)347:<711:SOSAE(>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR-ALPHA; HAMSTER OVARY CELLS; PROTEOLYTIC RELEASE; METALLOPROTEASE INHIBITORS; JUXTAMEMBRANE CLEAVAGE; MEMBRANE-PROTEINS; MOLECULAR-CLONING; MALE-FERTILITY; PHORBOL ESTER; PRECURSOR;
Keywords:
juxtamembrane; metalloprotease; phorbol ester; secretase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Sturrock, ED Univ Cape Town, Dept Med Biochem, ZA-7700 Rondebosch, South Africa Univ Cape Town Rondebosch South Africa ZA-7700 South Africa
Citazione:
Z.L. Woodman et al., "Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites", BIOCHEM J, 347, 2000, pp. 711-718

Abstract

The somatic and testis isoforms of angiotensin-converting enzyme (ACE) areboth C-terminally anchored ectoproteins that are shed by an unidentified secretase. Although testis and somatic ACE both share the same stalk and membrane domains the latter was reported to be shed inefficiently compared with testis ACE, and this was ascribed to cleavage at an alternative site [Beldent, Michaud, Bonnefoy, Chauvet and Corvol (1995) J. Biol. Chem. 270, 28962-28969]. These differences constitute a useful model system of the regulation and substrate preferences of the ACE secretase, and hence we investigated this further. In transfected Chinese hamster ovary cells, human somatic ACE (hsACE) was indeed shed less efficiently than human testis ACE, and shedding of somatic ACE responded poorly to phorbol ester activation. However,using several analytical techniques, we found no evidence that the somaticACE cleavage site differed from that characterized in testis ACE. First, anti-peptide antibodies raised to specific sequences on either side of the reported cleavage site (Arg(1137)/Leu(1138)) clearly recognized soluble porcine somatic ACE, indicating that cleavage was C-terminal to Arg(1137). Second, a competitive ELISA gave superimposable curves for porcine plasma ACE, secretase-cleaved porcine somatic ACE (eACE), and trypsin-cleaved ACE, suggesting similar C-terminal sequences. Third, mass-spectral analyses of digests of released soluble hsACE or of eACE enabled precise assignments of the C-termini, in each case to Arg(1203). These data indicated that soluble human and porcine somatic ACE, whether generated in vivo or in vitro, have C-termini consistent with cleavage at a single site, the Arg(1203)/Ser(1204) bond, identical with the Arg(627)/Ser(628) site in testis ACE. In conclusion, the inefficient release of somatic ACE is not due to cleavage at an alternative stalk site, but instead supports the hypothesis that the testis ACE ectodomain contains a motif that activates shedding, which is occluded by the additional domain found in somatic ACE.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 06:21:50