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Molecular and Cellular Biology, February 1999, p. 1401-1409, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Single Amino Acid Substitution in the v-Eyk Intracellular Domain Results in Activation of Stat3 and Enhances Cellular Transformation

Daniel Besser,1,* Jacqueline F. Bromberg,2 James E. Darnell Jr.,2 and Hidesaburo Hanafusa1

Laboratory of Molecular Oncology1 and Laboratory of Molecular Cell Biology,2 The Rockefeller University, New York, New York 10021

Received 10 August 1998/Returned for modification 9 October 1998/Accepted 27 October 1998

The receptor tyrosine kinase Eyk, a member of the Axl/Tyro3 subfamily, activates the STAT pathway and transforms cells when constitutively activated. Here, we compared the potentials of the intracellular domains of Eyk molecules derived from c-Eyk and v-Eyk to transform rat 3Y1 fibroblasts. The v-Eyk molecule induced higher numbers of transformants in soft agar and stronger activation of Stat3; levels of Stat1 activation by the two Eyk molecules were similar. A mutation in the sequence Y933VPL, present in c-Eyk, to the v-Eyk sequence Y933VPQ led to increased activation of Stat3 and increased transformation efficiency. However, altering another sequence, Y862VNT, present in both Eyk molecules to F862VNT markedly decreased transformation without impairing Stat3 activation. These results indicate that activation of Stat3 enhances transformation efficiency and cooperates with another pathway to induce transformation.

* Corresponding author. Mailing address: The Rockefeller University, Laboratory of Molecular Oncology, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8805. Fax: (212) 327-7943. E-mail: besserd{at}rockvax.rockefeller.edu.

Molecular and Cellular Biology, February 1999, p. 1401-1409, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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