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Cleavage of the Interleukin-11 receptor induces processing of its C-terminal fragments by the gamma-secretase and the proteasome.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Sep 16; Vol. 491 (2), pp. 296-302. Date of Electronic Publication: 2017 Jul 20. - Publication Year :
- 2017
-
Abstract
- 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- ADAM10 Protein genetics
ADAM10 Protein immunology
Amyloid Precursor Protein Secretases genetics
Amyloid Precursor Protein Secretases immunology
Animals
Cell Line, Tumor
Cell Membrane immunology
Cell Membrane metabolism
Gene Expression
Interleukin-11 genetics
Interleukin-11 immunology
Ligands
Membrane Proteins genetics
Membrane Proteins immunology
Mice
Peptide Fragments genetics
Peptide Fragments immunology
Peptide Fragments metabolism
Precursor Cells, B-Lymphoid cytology
Precursor Cells, B-Lymphoid immunology
Protein Binding
Proteolysis
Receptors, Interleukin-11 genetics
Receptors, Interleukin-11 immunology
Signal Transduction
ADAM10 Protein metabolism
Amyloid Precursor Protein Secretases metabolism
Interleukin-11 metabolism
Membrane Proteins metabolism
Precursor Cells, B-Lymphoid metabolism
Proteasome Endopeptidase Complex metabolism
Receptors, Interleukin-11 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 491
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 28735867
- Full Text :
- https://doi.org/10.1016/j.bbrc.2017.07.106