Protein Kinase A-mediated 14-3-3 Association Impedes Human Dapper1 to Promote Dishevelled Degradation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Jan 26

PMID 21262972

Citations 13

Authors

Hua Chen

Linhua Liu

Benyu Ma

Ting Martin Ma

Jun-Jie Hou

Guo-Ming Xie

Wei Wu

Fu-Quan Yang

Ye-Guang Chen

Affiliations

Soon will be listed here.

Abstract

Wnt signaling regulates embryo development and tissue homeostasis, and its deregulation leads to an array of diseases, including cancer. Dapper1 has been shown to be a key negative regulator of Wnt signaling. However, its function and regulation remain poorly understood. In this study, we report that 14-3-3β interacts with human Dapper1 (hDpr1). The interaction is dependent on protein kinase A (PKA)-mediated phosphorylation of hDpr1 at Ser-237 and Ser-827. 14-3-3β binding attenuates the ability of hDpr1 to promote Dishevelled (Dvl) degradation, thus enhancing Wnt signaling. We further provide evidence that PKA-mediated Dpr1 phosphorylation may contribute to growth and tumor formation of colon cancer Caco2 cells. Finally, we show that cyclooxygenase-2 expression and PKA activation are positively correlated with Dvl protein levels in colon cancer samples. Together, our findings establish a novel layer of regulation of Wnt signaling by PKA via the 14-3-3-Dpr1-Dvl axis.

Citing Articles

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