Zl. Fei et al., ASSOCIATION OF INSULIN-RECEPTOR SUBSTRATE-1 WITH SIMIAN-VIRUS-40 LARGE T-ANTIGEN, Molecular and cellular biology, 15(8), 1995, pp. 4232-4239
Mouse embryo cells expressing a wild-type number of insulin-like growt
h factor I receptors (IGF-IR) (W cells) can be transformed either by s
imian virus 40 large T antigen (SV40 T) or by overexpressed insulin re
ceptor substrate 1 (IRS-1), singly transfected. Neither SV40 T antigen
nor IRS-1, individually, can transform mouse embryo cells with a targ
eted disruption of the IGF-IR genes (R(-) cells). However, cotransfect
ion of SV40 T antigen and IRS-1 does transform R(-) cells. In this stu
dy, using different antibodies and different cell lines, we found that
SV40 T antigen and IRS-1 are coprecipitated from cell lysates in a sp
ecific fashion, regardless of whether the lysates are immunoprecipitat
ed with an antibody to SV40 T antigen or an antibody to IRS-1. The sam
e antibody to SV40 T antigen, however, fails to coprecipitate another
substrate ofIGF-IR, the transforming protein She, and two other signal
-transducing molecules, Grb2 and Sos. Finally, an SV40 T antigen lacki
ng the amino-terminal 250 amino acids fails to coprecipitate IRS-1 and
also fails to transform R(-) cells overexpressing mouse IRS-1. These
experiments indicate that IRS-1 associates with SV40 T antigen and tha
t this association plays a critical role in the combined ability of th
ese proteins to transform R(-) cells, This finding is discussed in lig
ht of the crucial role of the IGF-IR in the establishment and maintena
nce of the transformed phenotype.