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The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases

V Volmat1, M Camps, S Arkinstall

  • 1Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR-6543, Centre Antoine Lacassagne, 06189 Nice, France. volmat@unice.fr

Journal of Cell Science
|October 30, 2001
PubMed

Insights

Nuclear translocation is key for mitogenic signaling. During prolonged stimulation, p42/p44 MAPKs (extracellular signal-regulated kinases) inactivate within the nucleus, terminating the signal.

Area of Science:

  • Cellular Biology
  • Molecular Signaling

Background:

  • Nuclear translocation of p42/p44 MAPKs (extracellular signal-regulated kinases, ERKs) is essential for mitogenic signaling.
  • Understanding the mechanisms of signal termination is crucial for comprehending cellular responses.

Purpose of the Study:

  • To investigate the fate and regulation of p42/p44 MAPKs within the nucleus during long-term stimulation.
  • To identify the phosphatases responsible for nuclear inactivation of p42/p44 MAPKs.

Main Methods:

  • Phospho-specific immunostaining to monitor MAPK inactivation.
  • Assessing dephosphorylation of nuclear substrates like HIF-1 alpha.
  • Investigating phosphatase characteristics (synthesis, specificity, interaction).

Main Results:

  • p42/p44 MAPKs accumulate and become inactivated in the nucleus during long-term stimulation.
  • Nuclear inactivation is mediated by newly synthesized tyrosine or dual-specificity phosphatases, potentially MKP1/2.
  • p42/p44 MAPKs exhibit continuous shuttling between cytoplasm and nucleus.

Conclusions:

  • The nucleus serves as a critical site for terminating mitogenic signaling by sequestering p42/p44 MAPKs and facilitating their dephosphorylation by nuclear phosphatases.
  • Nuclear sequestration removes activated MAPKs from cytoplasmic activators like MEK.
  • Specific nuclear phosphatases play a key role in signal resolution.

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