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PMID: 15923620 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Active Src elevates the expression of beta-catenin by enhancement of cap-dependent translation.

Molecular and cellular biology ·Vol. 25 ·No. 12 ·2005-06-00 ·Pages 5031-9

Karni R, Gus Y, Dor Y, Meyuhas O, Levitzki A

Abstract

The proto-oncogene pp60(c-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 beta-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 beta-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.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Carrier Proteins/genetics,metabolism Cell Cycle Proteins Cell Line Cytoskeletal Proteins/genetics,metabolism Eukaryotic Initiation Factor-4E/genetics,metabolism Eukaryotic Initiation Factors Extracellular Signal-Regulated MAP Kinases/genetics,metabolism Gene Expression Regulation Genes, Reporter Humans MAP Kinase Kinase 1/genetics,metabolism Mice Phosphatidylinositol 3-Kinases/genetics,metabolism Phosphoproteins/genetics,metabolism Phosphorylation Protein Biosynthesis Protein Kinases/genetics,metabolism Proto-Oncogene Mas Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors,genetics,metabolism RNA Caps Ribosomal Protein S6/genetics,metabolism TOR Serine-Threonine Kinases Trans-Activators/genetics,metabolism beta Catenin
Chemicals
Adaptor Proteins, Signal Transducing CTNNB1 protein, human CTNNB1 protein, mouse Carrier Proteins Cell Cycle Proteins Cytoskeletal Proteins EIF4EBP1 protein, human Eif4ebp1 protein, mouse Eukaryotic Initiation Factor-4E Eukaryotic Initiation Factors MAS1 protein, human Phosphoproteins Proto-Oncogene Mas RNA Caps Ribosomal Protein S6 Trans-Activators beta Catenin Protein Kinases MTOR protein, human mTOR protein, mouse Proto-Oncogene Proteins pp60(c-src) TOR Serine-Threonine Kinases Extracellular Signal-Regulated MAP Kinases MAP Kinase Kinase 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Karni Rotem
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Gus Yael
Dor Yuval
Meyuhas Oded
Levitzki Alexander
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.12.5031-5039.2005
Published
2005-06-00
Pages
5031-9
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1140589
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.25.12.5031-5039.2005 PMC Full Text View journal details
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