Autophosphorylation of MAP kinase disables the MAPK pathway in apoptotic Xenopus eggs

Alexander A Tokmakov1, Kousuke Akino2, Sho Iguchi3

  • 1Faculty of Life Sciences, Kyoto Sangyo University, Japan.

Insights

Mitogen-activated protein kinases (MAPKs) are phosphorylated during apoptosis in Xenopus eggs, but this does not activate the enzyme. Intracellular acidification inactivates MAPKs, disabling survival pathways.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Apoptosis research

Background:

  • Mitogen-activated protein kinases (MAPKs) regulate crucial cellular processes like survival and apoptosis.
  • Understanding MAPK regulation during programmed cell death is essential.

Purpose of the Study:

  • To investigate the phosphorylation status and activity of Xenopus p42 MAPK during egg apoptosis.
  • To elucidate the role of intracellular pH in MAPK regulation during apoptosis.

Main Methods:

  • Utilized phosphorylation residue-specific antibodies to identify MAPK modification sites.
  • Analyzed MAPK phosphorylation and activity under varying pH conditions in vitro.
  • Observed intracellular pH changes in apoptotic Xenopus eggs.

Main Results:

  • Xenopus p42 MAPK is phosphorylated on a Tyr residue in the activation segment during egg apoptosis, but remains inactive.
  • MAPK phosphorylation coincides with significant intracellular acidification in apoptotic eggs.
  • Low pH stimulates MAPK autophosphorylation but inhibits substrate phosphorylation, leading to MAPK inactivation.

Conclusions:

  • Intracellular acidification during apoptosis inactivates MAPKs by disabling the MAPK-mediated survival pathway.
  • MAPK pathway shutdown and autophosphorylation stimulation under acidic conditions may be a universal feature of apoptotic cell death.

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