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A coupled chemical-genetic and bioinformatic approach to Polo-like kinase pathway exploration.

Protein phosphorylation is a ubiquitous mechanism for cellular signal propagation, and signaling network complexity presents a challenge to protein kinase substrate identification. Few targets of Polo-like kinases are known, despite their significant role in coordinating cell-cycle progression. Here, we combine chemical-genetic, bioinformatic, and proteomic tools for Polo-like kinase substrate identification. Specific pharmacological inhibition of budding yeast Polo-like kinase, Cdc5, resulted in a misaligned preanaphase spindle and subsequently delayed anaphase nuclear migration, revealing a Cdc5 function. A cellular screen for Cdc5 substrates identified Spc72, a spindle pole body (SPB) component and microtubule anchor required for nuclear positioning. Spc72 bound to the Cdc5 PBD in a mitosis-specific manner, was phosphorylated by Cdc5 in vitro, and demonstrated a loss of mitotic phosphorylation in vivo upon Cdc5 inhibition. Finally, an examination of Cdc5 binding by SPB-localized proteins expanded our knowledge of Cdc5 function at the SPB.

Pubmed ID: 18022565


  • Snead JL
  • Sullivan M
  • Lowery DM
  • Cohen MS
  • Zhang C
  • Randle DH
  • Taunton J
  • Yaffe MB
  • Morgan DO
  • Shokat KM


Chemistry & biology

Publication Data

November 20, 2007

Associated Grants

  • Agency: NCI NIH HHS, Id: 5T32CA09270
  • Agency: NIAID NIH HHS, Id: AI44009
  • Agency: NIBIB NIH HHS, Id: EB001987
  • Agency: NIGMS NIH HHS, Id: GM53270
  • Agency: NIGMS NIH HHS, Id: GM60594
  • Agency: NIGMS NIH HHS, Id: GM71434
  • Agency: NIAID NIH HHS, Id: R01 AI044009
  • Agency: NIAID NIH HHS, Id: R01 AI044009-10
  • Agency: NIBIB NIH HHS, Id: R01 EB001987
  • Agency: NIBIB NIH HHS, Id: R01 EB001987-13
  • Agency: NIGMS NIH HHS, Id: R01 GM053270

Mesh Terms

  • Alleles
  • Cell Cycle Proteins
  • Computational Biology
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Saccharomyces cerevisiae Proteins
  • Substrate Specificity