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