Okadaic Acid: a tool to study the hippo pathway

Mar Drugs. 2013 Mar 14;11(3):896-902. doi: 10.3390/md11030896.

Abstract

Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are activated in NIH3T3 cells exposed to okadaic acid. The Hippo pathway is a newly emerging signaling that functions as a tumor suppressor. MST1 and MST2 work as core kinases of the Hippo pathway and their activities depend on the autophosphorylation, which is negatively regulated by protein phosphatase 2A (PP2A). Okadaic acid has been frequently used to enhance the phosphorylation of MST1 and MST2 and to trigger the activation of the Hippo pathway. However other components of the Hippo pathway could also be targets of okadaic acid. In this review we first briefly summarize the molecular architecture of the Hippo pathway for the reference of researchers outside the field. We explain how MST kinases are regulated by PP2A and how okadaic acid activates MST2. Thereafter we discuss which components of the Hippo pathway are candidate substrates of protein phosphatases and which points we need to consider in the usage of okadaic acid to study the Hippo pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Okadaic Acid / pharmacology*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism
  • Protein-Serine-Threonine Kinases / drug effects*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects

Substances

  • Okadaic Acid
  • Stk4 protein, mouse
  • Hippo protein, mouse
  • Mst2 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2