CKIε/discs overgrown Promotes Both Wnt-Fz/β-Catenin and Fz/PCP Signaling in Drosophila

Thomas J. Klein, Andreas Jenny, Alexandre Djiane, Marek Mlodzik

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The related Wnt-Frizzled(Fz)/β-catenin and Fz/planar cell polarity (PCP) pathways are essential for the regulation of numerous developmental processes and are deregulated in many human diseases. Both pathways require members of the Dishevelled (Dsh or Dvl) family of cytoplasmic factors for signal transduction downstream of the Fz receptors. Dsh family members have been studied extensively, but their activation and regulation remains largely unknown. In particular, very little is known about how Dsh differentially signals to the two pathways. Recent work in cell culture has suggested that phosphorylation of Dsh by Casein Kinase I epsilon (CKIε) may act as a molecular "switch," promoting Wnt/β-catenin while inhibiting Fz/PCP signaling [1]. Here, we demonstrate in vivo in Drosophila through a series of loss-of-function and coexpression assays that CKIε acts positively for signaling in both pathways, rather than as a switch. Our data suggest that the kinase activity of CKIε is required for peak levels of Wnt/β-catenin signaling. In contrast, CKIε is a mandatory signaling factor in the Fz/PCP pathway, possibly through a kinase-independent mechanism. Furthermore, we have identified the primary kinase target residue of CKIε on Dsh. Thus, our data suggest that CKIε modulates Wnt/β-catenin and Fz/PCP signaling pathways via kinase-dependent and -independent mechanisms.

Original languageEnglish (US)
Pages (from-to)1337-1343
Number of pages7
JournalCurrent Biology
Volume16
Issue number13
DOIs
StatePublished - Jul 11 2006
Externally publishedYes

Fingerprint

Casein Kinase I
Catenins
Cell Polarity
Drosophila
phosphotransferases (kinases)
Phosphotransferases
Switches
Frizzled Receptors
Signal transduction
Phosphorylation
Cell culture
human diseases
signal transduction
cell polarity
non-specific serine/threonine protein kinase
Assays
Signal Transduction
phosphorylation
cell culture
Cell Culture Techniques

Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

CKIε/discs overgrown Promotes Both Wnt-Fz/β-Catenin and Fz/PCP Signaling in Drosophila. / Klein, Thomas J.; Jenny, Andreas; Djiane, Alexandre; Mlodzik, Marek.

In: Current Biology, Vol. 16, No. 13, 11.07.2006, p. 1337-1343.

Research output: Contribution to journalArticle

Klein, Thomas J. ; Jenny, Andreas ; Djiane, Alexandre ; Mlodzik, Marek. / CKIε/discs overgrown Promotes Both Wnt-Fz/β-Catenin and Fz/PCP Signaling in Drosophila. In: Current Biology. 2006 ; Vol. 16, No. 13. pp. 1337-1343.
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