Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P50583 (
asymmetrical
)
12,197
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In Drosophila neuroblasts (NBs), the
asymmetrical
localization and segregation of the cell-fate determinant Numb are regulated by its adaptor Partner of Numb (Pon) and the cell-cycle kinase Polo. Polo phosphorylates the Pon localization domain, thus leading to its basal distribution together with Numb, albeit through an unclear mechanism. Here, we find that Cdk1 phosphorylates Pon at Thr63, thus creating a docking site for the Polo-box domain (PBD) of
Polo-like kinase 1
(
Plk1
). The crystal structure of the
Plk1
PBD/phospho-Pon complex reveals that two phospho-Pon bound PBDs associate to form a dimer of dimers. We provide evidence that phospho-Pon binding-induced PBD dimerization relieves the autoinhibition of
Plk1
. Moreover, we demonstrate that the priming Cdk1 phosphorylation of Pon is important for sequential
Plk1
phosphorylation. Our results not only provide structural insight into how phosphoprotein binding activates
Plk1
but also suggest that binding to different phosphoproteins might mediate the fine-tuning of
Plk1
activity.
...
PMID:Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity. 2723 66
