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Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

MAP kinase phosphatase-1 is induced in abnormal fibers in inclusion body myositis

S Nakano1, A Shinde, H Ito

  • 1Department of Neurology, Kansai Medical University, Moriguchi-city, Japan. nakanos@takii.kmu.ac.jp

Neurology
|August 13, 2003
PubMed
Abstract

Insights

In inclusion body myositis (IBM), abnormal MKP-1 aggregates in muscle fibers likely inactivate ERK, suggesting ERK protein aggregation causes its apparent upregulation. MKP-1 is involved in myogenesis.

Area of Science:

  • Muscle biology
  • Cell signaling
  • Biochemistry

Background:

  • Upregulation of extracellular regulated kinase (ERK) in inclusion body myositis (IBM) vacuolated fibers is reported.
  • Mitogen-activated protein kinase (MAPK) kinases (MKK) activate MAPK, while MAPK phosphatases (MKP) inactivate MAPK.
  • MKP-1 plays a role in muscle fiber differentiation and is downregulated during myotube formation.

Purpose of the Study:

  • To investigate alterations in protein kinases and phosphatases regulating MAPK activity in sporadic inclusion body myositis (IBM).
  • To examine the role of MKP-1 and ERK in the pathogenesis of IBM.

Main Methods:

  • Immunolocalization of MKK1-4 and MKP-1-3 was performed on muscle specimens from 10 IBM patients and controls.
  • Colocalization studies were conducted to assess the relationship between MKP-1 and ERK in vacuolated fibers.

Main Results:

  • Strong, focal deposits of MKP-1 were observed in vacuolated fibers of IBM patients.
  • MKP-1 deposits colocalized with ERK in these fibers.
  • MKP-2, MKP-3, and MKK were not associated with vacuolated fibers.

Conclusions:

  • MKP-1 is abnormally induced in IBM vacuolated fibers, likely to inactivate ERK.
  • The absence of MKK activation suggests ERK protein aggregation, not upstream activators, causes its apparent upregulation in IBM.
  • MKP-1, like ERK, forms aggregates in vacuolated fibers and is implicated in myogenesis.

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