Fhit is a physiological target of the protein kinase Src
- Yuri Pekarsky*,
- Preston N. Garrison†,
- Alexey Palamarchuk*,
- Nicola Zanesi*,
- Rami I. Aqeilan*,
- Kay Huebner*,
- Larry D. Barnes†, and
- Carlo M. Croce*,‡
- *Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107; and †Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900
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Contributed by Carlo M. Croce, January 21, 2004
Abstract
The FHIT gene is a tumor suppressor that is frequently inactivated by genomic alterations at chromosomal region 3p14.2. In the last few years, a considerable amount of data describing inactivation of FHIT in a variety of human malignancies and demonstrating the tumor suppressor potential of Fhit have been reported. Despite the demonstration that FHIT functions as a tumor suppressor, the pathway through which Fhit induces apoptosis and inhibits growth of cancer cells is not known. Our data demonstrate that Fhit is a target of tyrosine phosphorylation by the Src protein kinase. We show that Src phosphorylates Y114 of Fhit in vitro and in vivo, providing insight into a biochemical pathway involved in Fhit signaling.
Footnotes
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↵ ‡ To whom correspondence should be addressed. E-mail: carlo.croce{at}mail.tju.edu.
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Abbreviations: MALDI-TOF, matrix-assisted laser desorption/ionization-time-of-flight; ESI, electrospray ionization.
- Copyright © 2004, The National Academy of Sciences
