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Publication : αE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway.

First Author  Li P Year  2016
Journal  Genes Dev Volume  30
Issue  7 Pages  798-811
PubMed ID  27013234 Mgi Jnum  J:232490
Mgi Id  MGI:5779445 Doi  10.1101/gad.274951.115
Citation  Li P, et al. (2016) alphaE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway. Genes Dev 30(7):798-811
abstractText  Cell-cell adhesion protein alphaE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that alphaE-catenin inhibits beta4 integrin-mediated activation of SRC tyrosine kinase.SRCis the first discovered oncogene, but the protein substrate critical for SRC-mediated transformation has not been identified. We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation. We uncovered a marked increase in this YAP1 phosphorylation in human and mouse SCC tumors with low/negative expression of alphaE-catenin. We demonstrate that the tumor suppressor function of alphaE-catenin involves negative regulation of the beta4 integrin-SRC signaling pathway and that SRC-mediated phosphorylation and activation of YAP1 are an alternative to the canonical Hippo signaling pathway that directly connect oncogenic tyrosine kinase signaling with YAP1.
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