In vivo expression of mutant pre-pro endothelins: Hierarchy of processing events but no strict requirement of Trp-Val at the processing site (Articolo in rivista)

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  • In vivo expression of mutant pre-pro endothelins: Hierarchy of processing events but no strict requirement of Trp-Val at the processing site (Articolo in rivista) (literal)
Anno
  • 1993-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1073/pnas.90.9.3923 (literal)
Alternative label
  • M.S. Fabbrini, A. Vitale, E. Pedrazzini, G. Nitti, M. Zamasi, M. Tamburin, V.R. Caiolfa, C. Patrono, L. Benatti (1993)
    In vivo expression of mutant pre-pro endothelins: Hierarchy of processing events but no strict requirement of Trp-Val at the processing site
    in Proc. natl. Acad. Sci. USA
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • M.S. Fabbrini, A. Vitale, E. Pedrazzini, G. Nitti, M. Zamasi, M. Tamburin, V.R. Caiolfa, C. Patrono, L. Benatti (literal)
Pagina inizio
  • 3923 (literal)
Pagina fine
  • 3927 (literal)
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  • http://www.pnas.org/content/90/9/3923.full.pdf+html (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 90 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • MSF, AV, EP: Consiglio Nazionale delle Ricerche - Istituto di Biologia e Biotecnologia Agraria Milano, Milan, Italy GN, LB, MZ, MT, VRC: Biotechnology and Cardiovascular Departments, Farmitalia Carlo Erba, Nerviano (MI) Italy CP: Laboratory of Cardiovascular Pharmacology, University of Chieti \"G. D'Annunzio\" School of Medicine, Chieti, Italy (literal)
Titolo
  • In vivo expression of mutant pre-pro endothelins: Hierarchy of processing events but no strict requirement of Trp-Val at the processing site (literal)
Abstract
  • Endothelin-1 (ET-1), a 21-residue vasoconstrictor peptide, originates in human cells from a 212-amino acid precursor (preproET-1). Big ET-1, an intermediate form of 38 amino acids, is generated by cleavage at basic-pair residues of proET-1, while a specific \"ET-converting enzyme\" was proposed to process the unusual Trp-Val site at positions 21 and 22 of big ET-1. We have previously shown that expression of synthetic RNA encoding human preproET-1 in Xenopus oocytes results in secretion of putative ET-1 and big ET-1. Here, to further dissect the processing pathway of preproET-1, we designed and expressed in oocytes a set of preproET-1 mutants. Four mutants affecting the Trp-Val site always originated putative ET-1(s) at levels comparable to the wild type, suggesting that there is only a conformational requirement for cleavage at this site. An Arg -- Ile mutation at the basic-pair site after the C terminus of big ET-1 fully inhibited the formation of both big ET-1 and ET-1, indicating that processing at this site is an early event and that big ET-1 is an obligate intermediate for the synthesis of ET-1 in vivo. Also, a truncated mutant bearing a stop codon after the C terminus of the big ET-1 sequence was totally stable and further processed into mature big ET-1 and ET-1, indicating that the second part of the precursor is not necessary for maturation. (literal)
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