Drosophila casein kinase 2 (CK2) promotes warts protein to suppress Yorkie protein activity for growth control

J Biol Chem. 2014 Nov 28;289(48):33598-607. doi: 10.1074/jbc.M114.580456. Epub 2014 Oct 15.

Abstract

Drosophila Hippo signaling regulates Wts activity to phosphorylate and inhibit Yki in order to control tissue growth. CK2 is widely expressed and involved in a variety of signaling pathways. In this study we report that Drosophila CK2 promotes Wts activity to phosphorylate and inhibit Yki activity, which is independent of Hpo-induced Wts promotion. In vivo, CK2 overexpression suppresses hpo mutant-induced expanded (Ex) up-regulation and overgrowth phenotype, whereas it cannot affect wts mutant. Consistent with this, knockdown of CK2 up-regulates Hpo pathway target expression. We also found that Drosophila CK2 is essential for tissue growth as a cell death inhibitor as knockdown of CK2 in the developing disc induces severe growth defects as well as caspase3 signals. Taken together, our results uncover a dual role of CK2; although its major role is promoting cell survive, it may potentially be a growth inhibitor as well.

Keywords: Cell Signaling; Drosophila; Hippo Pathway; Phosphorylation; Tumor Promoter; Tumor Suppressor Gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • YAP-Signaling Proteins

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila
  • Casein Kinase II
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila