Fhit is a physiological target of the protein kinase Src.
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.
Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Yuri
Y
Pekarsky
Preston N
PN
Garrison
Alexey
A
Palamarchuk
Nicola
N
Zanesi
Rami I
RI
Aqeilan
Kay
K
Huebner
Larry D
LD
Barnes
Carlo M
CM
Croce
D016475:3T3 Cells; D017766:Acid Anhydride Hydrolases; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D019061:src-Family Kinases / Q000378:metabolism*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D019061:src-Family Kinases; D000099170:Bis(5'-adenosyl)triphosphatase