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Originally published In Press as doi:10.1074/jbc.M204658200 on June 12, 2002

J. Biol. Chem., Vol. 277, Issue 35, 32078-32085, August 30, 2002
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Nuclear Translocation of Insulin Receptor Substrate-1 by the Simian Virus 40 T Antigen and the Activated Type 1 Insulin-like Growth Factor Receptor*

Marco Prisco, Francesca Santini, Raffaele Baffa, Mingli Liu, Robert Drakas, An Wu, and Renato BasergaDagger

From the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

32D cells are a murine hemopoietic cell line that undergoes apoptosis upon withdrawal of interleukin-3 (IL-3) from the medium. 32D cells have low levels of the type 1 insulin-like growth factor (IGF-I) receptor and do not express insulin receptor substrate-1 (IRS-1) or IRS-2. Ectopic expression of IRS-1 delays apoptosis but cannot rescue 32D cells from IL-3 dependence. In 32D/IRS-1 cells, IRS-1 is detectable, as expected, in the cytosol/membrane compartment. The SV40 large T antigen is a nuclear protein that, by itself, also fails to protect 32D cells from apoptosis. Co-expression of IRS-1 with the SV40 T antigen in 32D cells results in nuclear translocation of IRS-1 and survival after IL-3 withdrawal. Expression of a human IGF-I receptor in 32D/IRS-1 cells also results in nuclear translocation of IRS-1 and IL-3 independence. The phosphotyrosine-binding domain, but not the pleckstrin domain, is necessary for IRS-1 nuclear translocation. Nuclear translocation of IRS-1 was confirmed in mouse embryo fibroblasts. These results suggest possible new roles for nuclear IRS-1 in IGF-I-mediated growth and anti-apoptotic signaling.

* This work was supported by Grants CA089640 and AG20956 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th St., 624 BLSB, Philadelphia, PA 19107. Tel.: 215-503-4507; Fax: 215-923-0249; E-mail: R_baserga@lac.jci.tju.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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