Residues 762-801 of PLD1 mediate the interaction with PED/PEA15 (Articolo in rivista)

Type
Label
  • Residues 762-801 of PLD1 mediate the interaction with PED/PEA15 (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1039/c005272h (literal)
Alternative label
  • Doti N; Cassese A; Marasco D; Paturzo F; Sabatella M; Viparelli F; Dathan N; Monti SM; Miele C; Formisano P; Beguinot F; Ruvo M (2010)
    Residues 762-801 of PLD1 mediate the interaction with PED/PEA15
    in Molecular bioSystems (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Doti N; Cassese A; Marasco D; Paturzo F; Sabatella M; Viparelli F; Dathan N; Monti SM; Miele C; Formisano P; Beguinot F; Ruvo M (literal)
Pagina inizio
  • 2039 (literal)
Pagina fine
  • 2048 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 6 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • CNR, Ist Biostrutture & Bioimmagini IBB, I-80134 Naples, Italy Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol, Naples, Italy Univ Naples Federico 2, Dipartimento Sci Biol, I-80134 Naples, Italy CNR, Ist Endocrinol & Oncol Sperimentale Gaetano Salva, Naples, Italy (literal)
Titolo
  • Residues 762-801 of PLD1 mediate the interaction with PED/PEA15 (literal)
Abstract
  • The interaction of Phospholipase D1 (PLD1) by its C-terminal domain D4 with PED/PEA15 has been indicated as a target for type 2 diabetes. PED/PEA15 is overexpressed in several tissues of individuals affected by type 2 diabetes and its overexpression in intact cells and in transgenic animal models impairs insulin regulation of glucose transport by a mechanism mediated by the interaction with D4 and the consequent increase of protein kinase C-alpha activity. Expression of D4 or administration of a peptide mimicking the PED/PEA15 region involved in this interaction to cells stably overexpressing PED/PEA15 reduces its interaction with PLD1, thereby lowering PKC-alpha activation and restoring normal glucose transport mediated by PKC-zeta. By using D4 deletion mutants, we have restricted the PLD1 region involved in PED/PEA15 interaction to an N-terminal fragment named D4alpha (residues 712-818). This region binds PED/PEA15 with the same efficacy as D4 (K(D) approximately 0.7 microM) and, when transfected in different PED/PEA15-overexpressing cells, it is able to reduce PKC-alpha activity and to restore the sensitivity of PKC-zeta to insulin stimulation, independently of the PI3K/Akt signalling. We also show that the effective disruption of the PED/PEA15-PLD1 interaction can restore the normal ERK1/2 signalling. Finally, using a set of overlapping peptides that cover the D4alpha region, we have further restricted the shortest PED/PEA15-binding site to a segment encompassing residues 762-801, suggesting that a quite limited binding interface mostly contributes to the interaction and can thus be a selective target for the design of effective antagonists. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


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