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Molecular and Cellular Biology, June 2005, p. 5031-5039, Vol. 25, No. 12
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.12.5031-5039.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Active Src Elevates the Expression of ß-Catenin by Enhancement of Cap-Dependent Translation{ddagger}

Rotem Karni,1,{dagger},§ Yael Gus,1,{dagger} Yuval Dor,2 Oded Meyuhas,3 and Alexander Levitzki1*

Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem,1 Department of Molecular Biology,2 Department of Biochemistry, Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel3

Received 26 September 2004/ Returned for modification 4 November 2004/ Accepted 3 March 2005

The proto-oncogene pp60c-Src (c-Src) is activated in many types of cancer and contributes to the transformed phenotype of the tumor, although its role is not yet fully understood. Here we report that active Src elevates the levels of ß-catenin by enhancing cap-dependent translation. Src induces phosphorylation of the eukaryotic initiation factor 4E via the Ras/Raf/ERK pathway and the phosphorylation of its inhibitor 4E-BP1 via the PI3K/mTOR pathway. Activated Src enhances the accumulation of nuclear ß-catenin and enhances its transcriptional activity, elevating target genes such as cyclin D1. This novel activation of the Wnt pathway by Src most probably contributes to the oncogenic phenotype of cancer cells.


* Corresponding author. Mailing address: Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel. Phone: 972-2-6585404. Fax: 972-2-6512958. E-mail: levitzki{at}vms.huji.ac.il.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

§ Present address: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724.

{dagger} R.K. and Y.G. contributed equally to this work.


Molecular and Cellular Biology, June 2005, p. 5031-5039, Vol. 25, No. 12
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.12.5031-5039.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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