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PNAS 101 (11): 3775-3779

Copyright © 2004 by the National Academy of Sciences.

Biochemistry

Fhit is a physiological target of the protein kinase Src

Yuri Pekarsky *, Preston N. Garrison {dagger}, Alexey Palamarchuk *, Nicola Zanesi *, Rami I. Aqeilan *, Kay Huebner *, Larry D. Barnes {dagger}, and Carlo M. Croce * {ddagger}

*Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107; and {dagger}Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900

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.

Abbreviations: MALDI-TOF, matrix-assisted laser desorption/ionization-time-of-flight; ESI, electrospray ionization.

{ddagger} To whom correspondence should be addressed. E-mail: carlo.croce{at}mail.tju.edu.

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