Active Src elevates the expression of beta-catenin by enhancement of cap-dependent translation.
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.
Karni
Rotem
R
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Gus
Yael
Y
Dor
Yuval
Y
Meyuhas
Oded
O
Levitzki
Alexander
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012315:RNA Caps; D038601:Ribosomal Protein S6 / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011494:Protein Kinases; D000090063:Proto-Oncogene Mas; D016392:Proto-Oncogene Proteins pp60(c-src); D012315:RNA Caps; D038601:Ribosomal Protein S6; D058570:TOR Serine-Threonine Kinases; D015534:Trans-Activators; D051176:beta Catenin; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C087000:EIF4EBP1 protein, human; C499527:Eif4ebp1 protein, mouse; C000715470:MAS1 protein, human; C546842:MTOR protein, human; C546843:mTOR protein, mouse