Homeodomain-interacting Protein Kinase Regulates Yorkie Activity to Promote Tissue Growth

Curr Biol. 2012 Sep 11;22(17):1582-6. doi: 10.1016/j.cub.2012.06.074. Epub 2012 Jul 26.

Abstract

The Hippo (Hpo) tumor suppressor pathway regulates tissue size by inhibiting cell proliferation and promoting apoptosis. The core components of the pathway, Hpo, Salvador, Warts (Wts), and Mats, form a kinase cascade to inhibit the activity of Yorkie (Yki), the transcriptional effector of the pathway. Homeodomain-interacting protein kinases (Hipks) are a family of conserved serine/threonine kinases that function as regulators of various transcription factors to regulate developmental processes including proliferation, differentiation, and apoptosis. Hipk can induce tissue overgrowth in Drosophila. We demonstrate that Hipk is required to promote Yki activity. Hipk affects neither Yki stability nor its subcellular localization. Moreover, hipk knockdown suppresses the overgrowth and target gene expression caused by hyperactive Yki. Hipk phosphorylates Yki and in vivo analyses show that Hipk's regulation of Yki is kinase-dependent. To our knowledge, this is the first kinase identified to positively regulate Yki.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Drosophila
  • Drosophila Proteins / analysis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / physiology*
  • Trans-Activators / analysis
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Wings, Animal / growth & development
  • Wings, Animal / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Yki protein, Drosophila
  • Protein Kinases
  • HIPK protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila