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

Hua Chen, Linhua Liu, Benyu Ma, Ting Martin Ma, Jun Jie Hou, Guo Ming Xie, Wei Wu, Fu Quan Yang, Ye Guang Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)14870-14880
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number17
DOIs
StatePublished - Apr 29 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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