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Proteomic Screen Finds pSer/pThr-Binding Domain Localizing Plk1 to Mitotic Substrates
Andrew E. H. Elia,12Lewis C. Cantley,2Michael B. Yaffe1*
We have developed a proteomic approach for identifying
phosphopeptide binding domains that modulate kinase-dependent signalingpathways. An immobilized library of partially degenerate
phosphopeptidesbiased toward a particular protein kinase
phosphorylation motifis used to isolate phospho-binding
domains that bind to proteinsphosphorylated by that
kinase. Applying this approach to cyclin-dependentkinases (Cdks), we
identified the polo-box domain (PBD) of themitotic kinase polo-like
kinase 1 (Plk1) as a specific phosphoserine(pSer) or phosphothreonine
(pThr) binding domain and determinedits optimal binding motif. This
motif is present in known Plk1substrates such as Cdc25, and an optimal
phosphopeptide containingthe motif disrupted PBD-substrate binding and
localization ofthe PBD to centrosomes. This finding reveals how Plk1
can localizeto specific sites within cells in response to Cdk
phosphorylationat those sites and provides a structural
mechanism for targetingthe Plk1 kinase domain to its substrates.
1 Center for Cancer Research, Department of
Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Division of Signal Transduction, Beth Israel
Deaconess Hospital, and Department of Cell Biology, Harvard Medical
School, Boston, MA 02215, USA.
*
To whom correspondence should be addressed. E-mail:
myaffe{at}mit.edu
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