EGF-Induced ERK Activation Promotes CK2-Mediated Disassociation of α-Catenin from β-Catenin and Transactivation of β-Catenin

Authors

Haitao Ji, University of Texas
Ji Wang, University of Texas
Heinz Nika, University of Texas
David Hawke, University of Texas
Susan Keezer, Cell Signaling Technology, Inc., Danvers, MA
Qingyuan Ge, Cell Signaling Technology, Inc., Danvers, MA
Bingliang Fang, University of Texas
Xuexun Fang, Jilin University, Changchun, China
Dexing Fang, University of Texas
David W. Litchfield, University of Western OntarioFollow
Kenneth Aldape, University of Texas
Zhimin Lu, University of Texas

Document Type

Article

Publication Date

11-25-2009

Journal

Molecular Cell

Volume

36

Issue

4

First Page

547

Last Page

559

URL with Digital Object Identifier

http://dx.doi.org/10.1016/j.molcel.2009.09.034

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.