Activation of beta-catenin-TCF-mediated transcription by non-receptor tyrosine kinase v-Src.
Activation of Wnt signaling is an early event in colorectal tumorigenesis, while aberrant activation of non-receptor tyrosine kinase c-Src occurs during tumor progression. Here, we show that v-Src and receptor tyrosine kinase ErbB2 activate beta-catenin-TCF-mediated transcription. The effect of v-Src was abrogated by a dominant-negative mutant of TCF and the tumor suppressor APC. Furthermore, the effect of v-Src was partially abrogated by a dominant-negative mutant of MAP kinase, suggesting that v-Src exerts its effect at least in part via the MAP kinase pathway. Our finding raises the possibility that aberrantly activated c-Src may enhance Wnt signaling and this may contribute to tumor progression.
Haraguchi
Keiko
K
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nishida
Ayumu
A
Ishidate
Takao
T
Akiyama
Tetsu
T
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D017491:Genes, APC; D006801:Humans; D020935:MAP Kinase Signaling System; D009154:Mutation; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D015688:Oncogene Protein pp60(v-src); D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C495270:CTNNB1 protein, human