[PDF][PDF] EGF-induced ERK activation promotes CK2-mediated disassociation of α-catenin from β-catenin and transactivation of β-catenin

H Ji, J Wang, H Nika, D Hawke, S Keezer, Q Ge… - Molecular cell, 2009 - cell.com
H Ji, J Wang, H Nika, D Hawke, S Keezer, Q Ge, B Fang, X Fang, D Fang, DW Litchfield
Molecular cell, 2009cell.com
Increased transcriptional activity of β-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 β-catenin and α-catenin,
thereby abrogating the inhibitory effect of α-catenin on β-catenin transactivation via CK2α-
dependent phosphorylation of α-catenin at S641. ERK2, which is activated by EGFR …
Summary
Increased transcriptional activity of β-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 β-catenin and α-catenin, thereby abrogating the inhibitory effect of α-catenin on β-catenin transactivation via CK2α-dependent phosphorylation of α-catenin at S641. ERK2, which is activated by EGFR signaling, directly binds to CK2α via the ERK2 docking groove and phosphorylates CK2α primarily at T360/S362, subsequently enhancing CK2α activity toward α-catenin phosphorylation. In addition, levels of α-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 α-catenin promotes β-catenin transactivation and tumor cell invasion. These findings highlight the importance of the crosstalk between EGFR and Wnt pathways in tumor development.
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