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Inclusion body myositis: expression of extracellular signal-regulated kinase and its substrate

S Nakano1, A Shinde, S Kawashima

  • 1Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. snakano@isola.kuhp.kyoto-u.ac.jp

Neurology
|January 10, 2001
PubMed
Abstract

Insights

Intracellular signal transduction is impaired in inclusion body myositis (IBM). Extracellular signal-regulated kinase (ERK) accumulates in the cytoplasm, preventing nuclear transport in affected muscle cells.

Area of Science:

  • Cell biology
  • Molecular biology
  • Neuromuscular disorders

Background:

  • Mitogen-activated protein kinases (MAPKs) are crucial for cell signaling, regulating growth and differentiation.
  • Activated MAPKs normally move from the cytoplasm to the nucleus.

Purpose of the Study:

  • To investigate abnormal intracellular signal transduction in inclusion body myositis (IBM).
  • To assess the localization of MAPK family members in IBM.

Main Methods:

  • Examined extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 MAPK localization in IBM patients and controls.
  • Used bis-benzimide to test the relationship between immunopositive deposits and nuclei.

Main Results:

  • Vacuolated muscle fibers in IBM showed strong ERK immunoreactivity, but not JNK or p38.
  • ERK-positive deposits colocalized with Elk-1, an ERK nuclear substrate, on the nuclear surface in IBM vacuolated fibers.
  • Similar findings were noted in distal myopathy with rimmed vacuoles, but not in controls.

Conclusions:

  • Evidence suggests impaired transport of molecules to the nucleus in IBM vacuolated fibers.
  • This impairment may result from cytoplasmic aggregation of ERK and Elk-1 or abnormal nuclear pore function.

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