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Updated: May 15, 2026

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
12:47

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

Published on: December 27, 2016

Kinase-kinase interaction and modulation of tau phosphorylation

Mitsuko Hashiguchi1, Toshio Hashiguchi

  • 1Department of Physiology, Tokyo Medical University, Shinjuku, Tokyo, Japan. m-hasigu@tokyo-med.ac.jp

International Review of Cell and Molecular Biology
|January 1, 2013
PubMed

Insights

The tau phosphorylation protein complex (TPPC) regulates neuronal microtubule (MT) integrity by controlling tau phosphorylation. Understanding these protein interactions is key to tauopathies.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Microtubule (MT)-associated protein tau is crucial for neuronal MT network integrity.
  • Tau's binding activity and MT integrity are modulated by its phosphorylation state.
  • Kinase-phosphatase balance governs tau phosphorylation, requiring precise regulation of tau kinases and phosphatases.

Purpose of the Study:

  • To investigate the role of the tau phosphorylation protein complex (TPPC) in regulating tau phosphorylation.
  • To elucidate the topographical and temporal control mechanisms of tau kinases and phosphatases within the TPPC.
  • To understand how protein-protein interactions in TPPC impact MT functions and tau phosphorylation.

Main Methods:

  • Analysis of protein-protein interactions within the tau phosphorylation protein complex (TPPC).
  • Investigating the topographical and temporal regulation of tau kinases and phosphatases.
  • Studying the impact of kinase activity order and temporal modulation on tau phosphorylation states.

Main Results:

  • The TPPC anchors tau kinases and phosphatases, fulfilling topographical requirements for MT function.
  • Kinase switching dictates the order of kinase action, influencing tau phosphorylation.
  • Temporal modulation of kinase activity leads to differential tau phosphorylation states.

Conclusions:

  • Elucidating protein interactions in TPPC is vital for understanding tau phosphorylation regulation.
  • This knowledge sheds light on the physiological and pathological mechanisms of tau phosphorylation.
  • Targeting TPPC proteins offers potential strategies for maintaining MT functions and addressing tauopathies.

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