Systematic analysis of the Plk-mediated phosphoregulation in eukaryotes

Brief Bioinform. 2013 May;14(3):344-60. doi: 10.1093/bib/bbs041. Epub 2012 Jul 31.

Abstract

Substantial evidence has confirmed that Polo-like kinases (Plks) play a crucial role in a variety of cellular processes via phosphorylation-mediated signaling transduction. Identification of Plk phospho-binding proteins and phosphorylation substrates is fundamental for elucidating the molecular mechanisms of Plks. Here, we present an integrative approach for the analysis of Plk-specific phospho-binding and phosphorylation sites (p-sites) in proteins. From the currently available phosphoproteomic data, we predicted tens of thousands of potential Plk phospho-binding and phosphorylation sites in eukaryotes, respectively. Furthermore, statistical analysis suggested that Plk phospho-binding proteins are more closely implicated in mitosis than their phosphorylation substrates. Additional computational analysis together with in vitro and in vivo experimental assays demonstrated that human Mis18B is a novel interacting partner of Plk1, while pT14 and pS48 of Mis18B were identified as phospho-binding sites. Taken together, this systematic analysis provides a global landscape of the complexity and diversity of potential Plk-mediated phosphoregulation, and the prediction results can be helpful for further experimental investigation.

Keywords: GPS; PBD; phospho-binding; phosphorylation; polo-like kinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Eukaryotic Cells
  • Humans
  • Models, Biological
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • OIP5 protein, human
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1