Protein kinase C-alpha regulates insulin action and degradation by interacting with insulin receptor substrate-1 and 14-3-3epsilon. (Articolo in rivista)

Type
Label
  • Protein kinase C-alpha regulates insulin action and degradation by interacting with insulin receptor substrate-1 and 14-3-3epsilon. (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Alternative label
  • Oriente F; Andreozzi F; Romano C; Perruolo G; Perfetti A; Fiory F; Miele C; Beguinot F; Formisano P. (2005)
    Protein kinase C-alpha regulates insulin action and degradation by interacting with insulin receptor substrate-1 and 14-3-3epsilon.
    in The Journal of biological chemistry (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Oriente F; Andreozzi F; Romano C; Perruolo G; Perfetti A; Fiory F; Miele C; Beguinot F; Formisano P. (literal)
Pagina inizio
  • 40642 (literal)
Pagina fine
  • 40649 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 280 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Biologia e Patologia Cellulare e Molecolare and Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Federico II University of Naples, Italy (literal)
Titolo
  • Protein kinase C-alpha regulates insulin action and degradation by interacting with insulin receptor substrate-1 and 14-3-3epsilon. (literal)
Abstract
  • Protein kinase C (PKC)-alpha exerts a regulatory function on insulin action. We showed by overlay blot that PKC alpha directly binds a 180-kDa protein, corresponding to IRS-1, and a 30-kDa molecular species, identified as 14-3-3 epsilon. In intact NIH-3T3 cells overexpressing insulin receptors (3T3-hIR), insulin selectively increased PKC alpha coprecipitation with IRS-1, but not with IRS-2, and with 14-3-3 epsilon, but not with other 14-3-3 isoforms. Overexpression of 14-3-3 epsilon in 3T3-hIR cells significantly reduced IRS-1-bound PKC alpha activity, without altering IRS-1/PKC alpha co-precipitation. 14-3-3 epsilon overexpression also increased insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation, followed by increased activation of Raf1, ERK1/2, and Akt/protein kinase B. Insulin-induced glycogen synthase activity and thymidine incorporation were also augmented. Consistently, selective depletion of 14-3-3 epsilon by antisense oligonucleotides caused a 3-fold increase of IRS-1-bound PKC alpha activity and a similarly sized reduction of insulin receptor and IRS-1 tyrosine phosphorylation and signaling. In turn, selective inhibition of PKC alpha expression by antisense oligonucleotides reverted the negative effect of 14-3-3 epsilon depletion on insulin signaling. Moreover, PKC alpha inhibition was accompanied by a > 2-fold decrease of insulin degradation. Similar results were also obtained by overexpressing 14-3-3 epsilon. Thus, in NIH-3T3 cells, insulin induces the formation of multimolecular complexes, including IRS-1, PKC alpha, and 14-3-3 epsilon. The presence of 14-3-3 epsilon in the complex is not necessary for IRS-1/PKC alpha interaction but modulates PKC alpha activity, thereby regulating insulin signaling and degradation. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it