| Literature DB >> 19941816 |
Haitao Ji1, Ji Wang, Heinz Nika, David Hawke, Susan Keezer, Qingyuan Ge, Bingliang Fang, Xuexun Fang, Dexing Fang, David W Litchfield, Kenneth Aldape, Zhimin Lu.
Abstract
Increased transcriptional activity of beta-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation remains unclear. We demonstrate here that EGFR activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via CK2alpha-dependent phosphorylation of alpha-catenin at S641. ERK2, which is activated by EGFR signaling, directly binds to CK2alpha via the ERK2 docking groove and phosphorylates CK2alpha primarily at T360/S362, subsequently enhancing CK2alpha activity toward alpha-catenin phosphorylation. In addition, levels of alpha-catenin S641 phosphorylation correlate with levels of ERK1/2 activity in human glioblastoma specimens and with grades of glioma malignancy. This EGFR-ERK-CK2-mediated phosphorylation of alpha-catenin promotes beta-catenin transactivation and tumor cell invasion. These findings highlight the importance of the crosstalk between EGFR and Wnt pathways in tumor development.Entities:
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Year: 2009 PMID： 19941816 PMCID： PMC2784926 DOI： 10.1016/j.molcel.2009.09.034
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970