KIBRA protein phosphorylation is regulated by mitotic kinase Aurora and protein phosphatase 1

Ling Xiao, Yuanhong Chen, Ming Ji, Deanna J. Volle, Robert E. Lewis, Ming Ying Tsai, Jixin Dong

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Recent genetic studies in Drosophila identified Kibra as a novel regulator of the Hippo pathway, which controls tissue growth and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. The cellular function and regulation of human KIBRA remain largely unclear. Here, we show that KIBRA is a phosphoprotein and that phosphorylation of KIBRA is regulated in a cell cycle-dependent manner with the highest level of phosphorylated KIBRA detected in mitosis. We further demonstrate that the mitotic kinases Aurora-A and -B phosphorylate KIBRA both in vitro and in vivo. We identified the highly conserved Ser 539 as the primary phosphorylation site for Aurora kinases. Moreover, we found that wild-type, but not catalytically inactive, protein phosphatase 1 (PP1) associates with KIBRA. PP1 dephosphorylated Aurora-phosphorylated KIBRA. KIBRA depletion impaired the interaction between Aurora-A and PP1. We also show that KIBRA associates with neurofibromatosis type 2/Merlin in a Ser 539 phosphorylation-dependent manner. Phosphorylation of KIBRA on Ser 539 plays a role in mitotic progression. Our results suggest that KIBRA is a physiological substrate of Aurora kinases and reveal a new avenue between KIBRA/Hippo signaling and the mitotic machinery.

Original languageEnglish (US)
Pages (from-to)36304-36315
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number42
DOIs
StatePublished - Oct 21 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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