title: Insulin receptor substrates-5 and -6 are poor substrates for the insulin receptor.
abstract: Insulin receptor substrates (IRS)-5 and -6 are two recently identified members of the IRS family. We investigated their roles as insulin receptor substrates and compared them with Src-homology-2-containing (Shc) protein, a well-established substrate. Bioluminescence resonance energy transfer (BRET) experiments showed no interaction between the receptor and IRS-5, while interaction with IRS-6 was not enhanced by insulin. By contrast, Shc showed an insulin-induced BRET response, as did a truncated form of IRS-1 (1-262). While Shc was heavily phosphorylated after stimulation of the insulin receptor, IRS-5 and -6 showed very weak phosphorylation levels. These results suggest that, although these two adaptors have previously been proposed as substrates for the insulin receptor, they are poor substrates for the insulin receptor. This calls into question their relevance to insulin signalling.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium. soetkinversteyhe@gmail.com.
authors.forename: Soetkin
authors.initials: S
authors.lastname: Versteyhe
authors.forename: Christophe
authors.initials: C
authors.lastname: Blanquart
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hampe
authors.forename: Shaukat
authors.initials: S
authors.lastname: Mahmood
authors.forename: Nevena
authors.initials: N
authors.lastname: Christeff
authors.forename: Pierre
authors.initials: P
authors.lastname: De Meyts
authors.forename: Steven G
authors.initials: SG
authors.lastname: Gray
authors.forename: Tarik
authors.initials: T
authors.lastname: Issad