Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase

Mol Biol Cell. 2003 Apr;14(4):1489-500. doi: 10.1091/mbc.e02-09-0612.

Abstract

Aurora-B is a protein kinase required for chromosome segregation and the progression of cytokinesis during the cell cycle. We report here that Aurora-B phosphorylates GFAP and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by Aurora-B; Thr-7/Ser-13/Ser-38 of GFAP, and Thr-16 of desmin are common with those related to Rho-associated kinase (Rho-kinase), which has been reported to phosphorylate GFAP and desmin at cleavage furrow during cytokinesis. We identified Ser-59 of desmin to be a specific site phosphorylated by Aurora-B in vitro. Use of an antibody that specifically recognized desmin phosphorylated at Ser-59 led to the finding that the site is also phosphorylated specifically at the cleavage furrow during cytokinesis in Saos-2 cells. Desmin mutants, in which in vitro phosphorylation sites by Aurora-B and/or Rho-kinase are changed to Ala or Gly, cause dramatic defects in filament separation between daughter cells in cytokinesis. The results presented here suggest the possibility that Aurora-B may regulate cleavage furrow-specific phosphorylation and segregation of type III IFs coordinatedly with Rho-kinase during cytokinesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Binding Sites / genetics
  • COS Cells
  • Cell Division
  • Cell Line
  • Desmin / chemistry*
  • Desmin / genetics
  • Desmin / metabolism*
  • Glial Fibrillary Acidic Protein / chemistry
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • In Vitro Techniques
  • Intermediate Filaments / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serine / chemistry
  • rho-Associated Kinases

Substances

  • Desmin
  • Glial Fibrillary Acidic Protein
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Fusion Proteins
  • Serine
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases