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Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Human NDR kinases are rapidly activated by MOB proteins through recruitment to the plasma membrane and

Alexander Hergovich1, Samuel J Bichsel, Brian A Hemmings

  • 1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. brian.hemmings@fmi.ch.

Molecular and Cellular Biology
|September 2, 2005
PubMed

Insights

Human nuclear Dbf2-related kinases (NDRs) are primarily cytoplasmic but become active upon membrane recruitment. Co-expression with human MOBs further enhances NDR kinase activity at the plasma membrane.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Human nuclear Dbf2-related kinases (NDRs) are implicated in cancer but their functions and regulation are unclear.
  • NDRs are typically found in the cytoplasm in both active and inactive states.

Purpose of the Study:

  • To investigate the localization and activation mechanisms of human NDR kinases.
  • To explore the role of human MOBs (hMOBs) in NDR regulation in vivo.

Main Methods:

  • Immunofluorescence microscopy to observe NDR and hMOB localization.
  • Analysis of NDR phosphorylation at specific sites (Ser281, Thr444).
  • Use of chimeric hMOB molecules for inducible membrane translocation experiments.

Main Results:

  • Active and inactive human NDRs are predominantly cytoplasmic.
  • NDR kinases colocalize with hMOBs at the plasma membrane.
  • Membrane targeting of NDR leads to constitutive activation (phosphorylation at Ser281 and Thr444), further enhanced by hMOBs.
  • hMOBs promote NDR activation in vivo, dependent on their interaction and occurring at the membrane.
  • NDR phosphorylation and activation occur rapidly upon hMOB recruitment to the membrane.

Conclusions:

  • Human NDR kinases are activated through rapid recruitment to the plasma membrane mediated by hMOBs.
  • This membrane-associated activation mechanism provides new insights into NDR kinase regulation in vivo.

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