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

Biochem Biophys Res Commun. 2001 Oct 26;288(2):313-20. doi: 10.1006/bbrc.2001.5761.

Abstract

Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibit its ability to initiate apoptosis while preserving signaling events such as NF-kappaB activation. Therefore, we sought to determine if p42(mapk/erk2) was also capable of phosphorylating additional human death receptors within the TNF receptor superfamily. These studies showed that CD120a and DR3 are significantly phosphorylated by p42(mapk/erk2) but Fas, DR4 and DR5 are not. Additionally, we demonstrated that (i) the p42(mapk/erk2)-dependent phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal regions but not the death domains of CD120a and DR3, (iii) Ser 253 is a preferred site of phosphorylation on CD120a, and (iv) the p42(mapk/erk2)-dependent phosphorylation of the DR3 cytoplasmic domain occurred exclusively at non-p42/44(mapk/erk2/1) consensus sites. These findings suggest that human death receptors segregate into two groups along lines of phylogeny with respect to Ser/Thr phosphorylation by p42(mapk/erk2).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • COS Cells
  • Consensus Sequence
  • Cytoplasm / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Okadaic Acid / pharmacology
  • Phosphoamino Acids / analysis
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • fas Receptor / metabolism

Substances

  • Antigens, CD
  • Phosphoamino Acids
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFRSF25 protein, human
  • fas Receptor
  • Okadaic Acid
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate