Cleavage of the Interleukin-11 receptor induces processing of its C-terminal fragments by the gamma-secretase and the proteasome

Biochem Biophys Res Commun. 2017 Sep 16;491(2):296-302. doi: 10.1016/j.bbrc.2017.07.106. Epub 2017 Jul 20.


The cytokine Interleukin-11 (IL-11) signals through the membrane-bound IL-11 receptor (IL-11R), which is expressed in a cell-type specific manner. We have recently shown that the metalloprotease ADAM10 can cleave the IL-11R. The liberated soluble IL-11R (sIL-11R) ectodomain can bind its ligand, and the resulting IL-11/sIL-11R complex can activate cells that do not express the IL-11R (trans-signaling). In this study, we show that the remaining C-terminal fragment (CTF1) after ADAM10-mediated cleavage is subsequently cleaved within the membrane by the gamma-secretase complex, and that the resulting shorter CTF2 is further degraded by the proteasome. In contrast to other transmembrane receptors, e.g. Notch, we find no evidence that the IL-11R CTF can translocate into the nucleus to act as a transcription factor, suggesting that regulated intramembrane proteolysis of the IL-11R CTF acts as a mechanism to clear the plasma membrane from remaining protein fragments after cleavage of its ectodomain.

Keywords: Gamma-secretase; Interleukin-11; Interleukin-11 receptor; Proteasome; Proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM10 Protein / genetics
  • ADAM10 Protein / immunology
  • ADAM10 Protein / metabolism*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / immunology
  • Amyloid Precursor Protein Secretases / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Gene Expression
  • Interleukin-11 / genetics
  • Interleukin-11 / immunology
  • Interleukin-11 / metabolism*
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding
  • Proteolysis
  • Receptors, Interleukin-11 / genetics
  • Receptors, Interleukin-11 / immunology
  • Receptors, Interleukin-11 / metabolism*
  • Signal Transduction


  • Interleukin-11
  • Ligands
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Interleukin-11
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • Adam10 protein, mouse
  • Proteasome Endopeptidase Complex