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; Carlo M. Croce

doi:10.1073/pnas.0400481101

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, Carlo M. Croce^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

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.

Original language	English
Pages (from-to)	3775-3779
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	11
DOIs	https://doi.org/10.1073/pnas.0400481101
State	Published - 16 Mar 2004
Externally published	Yes

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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.",

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AU - Pekarsky, Yuri

AU - Garrison, Preston N.

AU - Palamarchuk, Alexey

AU - Zanesi, Nicola

AU - Aqeilan, Rami I.

AU - Huebner, Kay

AU - Barnes, Larry D.

AU - Croce, Carlo M.

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AB - 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.

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Fhit is a physiological target of the protein kinase Src

Abstract

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