p21-activated kinase 1 interacts with and phosphorylates histone H3 in breast cancer cells

Feng Li, Liana Adam, Ratna K. Vadlamudi, Hongyi Zhou, Subrata Sen, Jonathan Chernoff, Mahitosh Mandal, Rakesh Kumar

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Stimulation of p21-activated kinase-1 (Pak1) signaling promotes motility, invasiveness, anchorage-independent growth and abnormal mitotic assembly in human breast cancer cells. Here, we provide new evidence that, before the onset of mitosis, activated Pak1 is specifically localized with the chromosomes during prophase and on the centrosomes in metaphase and moves to the contraction ring during cytokinesis. To identify mitosis-specific substrate of Pak1, we screened a synchronized G2-M expression library by using a glutathione transferase Pak1 solid-phase-based kinase reaction. This analysis identified histone H3 as a substrate of Pak1 both in vitro and in vivo, and it specifically interacted with Pak1 but not Pak2 or Pak3. Site-directed mutagenesis indicated that Pak1 phosphorylates histone H3 on Ser10. Expressions of the wild-type, or catalytically active, Pak1 caused it to appear at the poles corresponding to mitotic centrosomes in a variety of mammalian cells. Together, these results suggest for the first time that Pak1 interacts with and phosphorylates histone H3 and may thus influence the Pak1-histone H3 pathway, which in turn may influence mitotic events in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)767-773
Number of pages7
JournalEMBO Reports
Volume3
Issue number8
DOIs
StatePublished - Aug 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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