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Heterogeneity in the phosphorylation of human death receptors by p42(mapk/erk2)

S K Frankel1, A A Van Linden, D W Riches

  • 1Program in Cell Biology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.

Biochemical and Biophysical Research Communications
|October 19, 2001
PubMed

Insights

p42(MAPK/ERK2) phosphorylates human CD120a and DR3 death receptors, affecting apoptosis signaling. This phosphorylation occurs on specific residues, differentiating receptors based on their response to this kinase.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • p42(MAPK/ERK2) phosphorylation of murine CD120a inhibits apoptosis initiation.
  • This phosphorylation preserves signaling pathways like NF-kappaB activation.

Purpose of the Study:

  • To investigate if p42(MAPK/ERK2) phosphorylates other human death receptors in the TNF receptor superfamily.
  • To identify which human death receptors are substrates for p42(MAPK/ERK2).

Main Methods:

  • Western blotting and phospho-specific antibodies to detect phosphorylation.
  • Site-directed mutagenesis to identify phosphorylation sites.
  • Analysis of TNF receptor superfamily members including CD120a, DR3, Fas, DR4, and DR5.

Main Results:

  • CD120a and DR3 were significantly phosphorylated by p42(MAPK/ERK2).
  • Fas, DR4, and DR5 were not phosphorylated by p42(MAPK/ERK2).
  • Phosphorylation occurred on Ser/Thr residues in membrane-proximal regions, not death domains, with Ser 253 being a key site on CD120a.

Conclusions:

  • Human death receptors can be categorized based on their susceptibility to p42(MAPK/ERK2)-mediated Ser/Thr phosphorylation.
  • p42(MAPK/ERK2) plays a role in regulating apoptosis signaling through differential phosphorylation of death receptors.

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