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FRAG1, a Gene that Potently Activates Fibroblast Growth Factor Receptor by C-Terminal Fusion through Chromosomal Rearrangement
Matthew V. Lorenzi, Yoshihiro Horii, Ryuya Yamanaka, Kazushige Sakaguchi and Toru Miki
Proceedings of the National Academy of Sciences of the United States of America
Vol. 93, No. 17 (Aug. 20, 1996), pp. 8956-8961
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/39983
Page Count: 6
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A constitutively active form of fibroblast growth factor 2 (FGFR2) was identified in rat osteosarcoma (ROS) cells by an expression cloning strategy. Unlike other tyrosine kinase receptors activated by N-terminal truncation in tumors, this receptor, FGFR2-ROS, contains an altered C terminus generated from chromosomal rearrangements with a novel gene, designated FGFR activating gene 1 (FRAG1). While the removal of the C terminus slightly activates FGFR2, the presence of the FRAG1 sequence drastically stimulates the transforming activity and autophosphorylation of the receptor. FGFR2-ROS is expressed as a unusually large protein and is highly phosphorylated in NIH 3T3 transfectants. FRAG1 is ubiquitously expressed and encodes a predicted protein of 28 kDa lacking significant structural similarity to known proteins. Epitope-tagged FRAG1 protein showed a perinuclear localization by immunofluorescence staining. The highly activated state of FGFR2-ROS appears to be attributed to constitutive dimer formation and higher phosphorylation level as well as possibly altered subcellular localization. These results indicate a unique mechanism of receptor activation by a C terminus alteration through a chromosomal fusion with FRAG1.
Proceedings of the National Academy of Sciences of the United States of America © 1996 National Academy of Sciences