alphaE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
(2016) Genes & Development — Vol. 30, n° 7, p. 798-811 (2016)
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- Abstract
- Cell-cell adhesion protein alphaE-catenin inhibits skin SCC development; however, the mechanisms responsible for this function are not completely understood. We report here that alphaE-catenin inhibits ß4 integrin-mediated activation of SRC tyrosine kinase. SRC is the first discovered oncogene, but the critical for SRC-mediated transformation protein substrate has not been identified. We found that YAP1, the pivotal effector of the Hippo signaling pathway, is the direct SRC phosphorylation target and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation. Our results reveal an alternative to Hippo signaling pathway, which directly connects oncogenic tyrosine kinase signaling with YAP1, and provide a mechanistic insight into the tumor suppressor activity of alphaE-catenin.
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Citations
Li, P., Silvis, M., Honaker, Y., Lien, W.-H., Arron, S. T., & Vasioukhin, V. (2016). alphaE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway. Genes & Development, 30(7), 798-811. https://doi.org/10.1101/gad.274951.115 (Original work published 2016)