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Does MK5 reconcile classical and atypical MAP kinases?

Maria Perander1, Stephen M Keyse, Ole-Morten Seternes

  • 1Department of Pharmacology, Institute of Medical Biology, University of Tromso, N-9037 Tromso, Norway.

Frontiers in Bioscience : a Journal and Virtual Library
|May 30, 2008
PubMed

Insights

MAP kinase-activated protein kinase 5 (MK5) is not activated by cellular stress like other related kinases. Instead, MK5 appears to be regulated by atypical MAP kinases ERK3 and ERK4, suggesting a distinct signaling role.

Area of Science:

  • Cellular signaling pathways
  • Protein kinase regulation
  • MAP kinase family

Background:

  • MAP kinase-activated protein kinase 5 (MK5), also known as PRAK, was initially identified as downstream of p38 MAP kinase.
  • MK5 shares sequence similarity with MK2 and MK3, which are activated by cellular stress and inflammatory cytokines.
  • However, MK5 does not exhibit activation in response to these stimuli.

Purpose of the Study:

  • To investigate the distinct activation and physiological function of MK5 compared to other MAPKAP kinases.
  • To explore the signaling pathways that regulate MK5 activity.
  • To understand the role of MK5 in cellular stress and inflammatory responses.

Main Methods:

  • Analysis of MK5 activation in response to cellular stress and inflammatory stimuli.
  • Phenotypic analysis of MK5-deficient (null) mice, including response to endotoxic shock and LPS-induced cytokine expression.
  • Investigation of MK5 complex formation with atypical MAP kinases ERK3 and ERK4.

Main Results:

  • MK5-deficient mice show normal responses to endotoxic shock and unchanged cytokine expression upon LPS challenge, unlike MK2/MK3 deficient mice.
  • MK5 is not activated by cellular stress or pro-inflammatory cytokines, despite its sequence similarity to MK2/MK3.
  • MK5 is uniquely regulated and activated through complex formation with atypical MAP kinases ERK3 and ERK4.

Conclusions:

  • MK5 functions distinctly from MK2 and MK3, as it is not activated by classical stress pathways.
  • MK5's unique regulation by ERK3 and ERK4 suggests it operates downstream of alternative signaling cascades.
  • This finding positions MK5 as a unique member of the MAPKAP kinase family with a potentially novel physiological role.

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