Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus

J Cell Sci. 2007 Nov 15;120(Pt 22):4060-70. doi: 10.1242/jcs.014795. Epub 2007 Oct 30.

Abstract

The chromosomal passenger complex (CPC) is a crucial regulator of chromosome, cytoskeleton and membrane dynamics during mitosis. Here, using liquid chromatography coupled to mass spectrometry (LC-MS), we identified phosphopeptides and phosphoprotein complexes recognized by a phosphorylation-specific antibody that labels the CPC. A mitotic phosphorylation motif {PX[G/T/S][L/M]S(P) P or WGLS(P) P} was identified by MS in 11 proteins, including FZR1 (Cdh1) and RIC8A-two proteins with potential links to the CPC. Phosphoprotein complexes contained the known CPC components INCENP, Aurora-B (Aurkb) and TD-60 (Rcc2, RCC1-like), as well as SMAD2, 14-3-3 proteins, PP2A and Cdk1 (Cdc2a), a probable kinase for this motif. Protein sequence analysis identified phosphorylation motifs in additional proteins, including SMAD2, PLK3 and INCENP. Mitotic SMAD2 and PLK3 phosphorylation was confirmed using phosphorylation-specific antibodies, and, in the case of Plk3, phosphorylation correlated with its localization to the mitotic apparatus and the midbody. A mutagenesis approach was used to show that INCENP phosphorylation is required for its localization to the midbody. These results provide evidence for a shared phosphorylation event that regulates localization of crucial proteins during mitosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Chromosomal Proteins, Non-Histone / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Mitosis*
  • Molecular Sequence Data
  • Peptides / chemistry
  • Phosphoproteins / chemistry
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Transport
  • Proteomics
  • Reproducibility of Results
  • Spindle Apparatus / metabolism*
  • Tumor Suppressor Proteins

Substances

  • Antibodies, Monoclonal
  • Chromosomal Proteins, Non-Histone
  • INCENP protein, human
  • Peptides
  • Phosphoproteins
  • Tumor Suppressor Proteins
  • PLK3 protein, human
  • Protein Serine-Threonine Kinases