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Originally published In Press as doi:10.1074/jbc.M202956200 on April 4, 2002

J. Biol. Chem., Vol. 277, Issue 25, 22798-22805, June 21, 2002
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c-Src-dependent Transcriptional Activation of TFII-I*

Venugopalan CheriyathDagger , Zana Patrick Desgranges§, and Ananda L. RoyDagger §||

From the Dagger  Department of Pathology and Programs in § Immunology and  Genetics, Tufts University School of Medicine, Boston, Massachusetts 02111

TFII-I is a multifunctional transcription factor that is also involved in signal transduction. Here we show that TFII-I undergoes a c-Src-dependent tyrosine phosphorylation on tyrosine residues 248 and 611 and translocates to the nucleus in response to growth factor signaling. Tyrosine-phosphorylated nuclear TFII-I activates a stably integrated c-fos reporter gene. Withdrawal of signal leads to diminution of nuclear TFII-I, suggesting that the signal-dependent translocation is reversible. Antibodies against either TFII-I or c-Src abrogate growth factor-stimulated activation of c-fos. Consistent with the notion that tyrosine phosphorylation of TFII-I is required for its transcriptional activity, phosphorylation-deficient mutants of TFII-I fail to activate the c-fos promoter. These data demonstrate that TFII-I, through a Src-dependent mechanism, reversibly translocates from the cytoplasm to the nucleus, leading to the transcriptional activation of growth-regulated genes.


* This work was supported by National Institutes of Health Grant AI45150 (to A. L. R.).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: Dept. of Pathology and Programs in Immunology and Genetics, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Tel.: 617-636-6715; Fax: 17-636-2990; E-mail: ananda.roy@tufts.edu.


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