IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1. (Articolo in rivista)

Type
Label
  • IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1. (Articolo in rivista) (literal)
Anno
  • 2001-01-01T00:00:00+01:00 (literal)
Alternative label
  • Miranda C. 1, Greco A. 2, Miele C. 1-3, Pierotti M.A. 2, Van Obberghen E. 1 (2001)
    IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1.
    in Journal of cellular physiology (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Miranda C. 1, Greco A. 2, Miele C. 1-3, Pierotti M.A. 2, Van Obberghen E. 1 (literal)
Pagina inizio
  • 35 (literal)
Pagina fine
  • 46 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 186 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1. (literal)
Abstract
  • TRK-T1 oncogene is generated by the rearrangement of the NGF receptor TrkA with TPR. This gives rise to the constitutive tyrosine autophosphorylation and activation of the kinase. To study TRK-T1 oncogenic signaling and compare it to that induced by the genuine receptor TrkA, we investigated the involvement of IRS-1, a docking protein implicated in mitogenic signaling induced by several growth factors, in TRK-T1 and TrkA signaling. Here, we show that IRS-1 and IRS-2 are phosphorylated on tyrosine in presence of both TRK-T1 and the activated TrkA receptor. These tyrosine phosphorylations lead to IRS-1- and IRS-2-induced recruitment of p85PI3K, SHP-2, and Grb2 and increase in PI 3-kinase activity associated with IRS-1. Furthermore, we found that TRK-T1 is able to activate c-fos serum responsive element in cooperation with IRS-1 and IRS-2. We observed that TRK-T1 stimulates DNA synthesis in wild-type fibroblasts but not in IRS-1(-/-) mouse embryo fibroblasts. Yeast two-hybrid system experiments showed the occurrence of direct interaction between TRK and IRS molecules, which suggests involvement of different modes of interactions. On the whole, our results suggest that IRS-1 and IRS-2 could be substrates of TRK-T1 and TrkA, and hence could participate in their signal generation. (literal)
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