Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates Academic Article uri icon

Overview

MeSH Major

  • Phosphopeptides
  • Phosphoserine
  • Phosphothreonine
  • Protein Kinases
  • Protein Structure, Tertiary
  • cdc25 Phosphatases

abstract

  • We have developed a proteomic approach for identifying phosphopeptide binding domains that modulate kinase-dependent signaling pathways. An immobilized library of partially degenerate phosphopeptides biased toward a particular protein kinase phosphorylation motif is used to isolate phospho-binding domains that bind to proteins phosphorylated by that kinase. Applying this approach to cyclin-dependent kinases (Cdks), we identified the polo-box domain (PBD) of the mitotic kinase polo-like kinase 1 (Plk1) as a specific phosphoserine (pSer) or phosphothreonine (pThr) binding domain and determined its optimal binding motif. This motif is present in known Plk1 substrates such as Cdc25, and an optimal phosphopeptide containing the motif disrupted PBD-substrate binding and localization of the PBD to centrosomes. This finding reveals how Plk1 can localize to specific sites within cells in response to Cdk phosphorylation at those sites and provides a structural mechanism for targeting the Plk1 kinase domain to its substrates.

publication date

  • February 21, 2003

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1079079

PubMed ID

  • 12595692

Additional Document Info

start page

  • 1228

end page

  • 31

volume

  • 299

number

  • 5610