Protein kinase A-mediated 14-3-3 association impedes human Dapper1 to promote Dishevelled degradation

  • Chen H
  • Liu L
  • Ma B
 et al. 
  • 23

    Readers

    Mendeley users who have this article in their library.
  • 12

    Citations

    Citations of this article.

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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Hua Chen

  • Linhua Liu

  • Benyu Ma

  • Ting Martin Ma

  • Jun Jie Hou

  • Guo Ming Xie

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free