Reference : Three dileucine-like motifs within the interbox1/2 region of the human oncostatin M r...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Three dileucine-like motifs within the interbox1/2 region of the human oncostatin M receptor prevent efficient surface expression in the absence of an associated Janus kinase
Radtke, S. [> >]
Jörissen, A. [> >]
de Leur, H. S. [> >]
Heinrich, P. C. [> >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBilu)
[en] Amino Acid Motifs ; Receptors, Cytokine ; Protein-Tyrosine Kinases ; Molecular Sequence Data ; Leucine ; Janus Kinase 1 ; Hydrophobicity ; Humans ; Half-Life ; Cercopithecus aethiops ; COS Cells ; Animals ; Amino Acid Sequence ; Receptors, Oncostatin M
[en] The oncostatin M receptor (OSMR) is part of receptor complexes for oncostatin M and interleukin-31. Signaling events are triggered by Jaks (Janus kinases) that constitutively bind to membrane-proximal receptor regions. Besides their established role in signaling, Jaks are involved in the regulation of the surface expression of several cytokine receptors. Here, we analyzed the structural requirements within the human OSMR that underlie its limited surface expression in the absence of associated Jaks. We identified three dileucine-like motifs within the Jak-binding region of the OSMR that control receptor surface and overall expression. A receptor mutant in which all three motifs were mutated to alanine displayed markedly increased surface expression. Although the surface half-life of this mutant was increased compared with that of the wild-type receptor, no difference in the internalization rate was detectable, implying that these receptors differ in their post-endocytic fate. The protein stability of the wild-type receptor was markedly lower than that of mutant receptors, but could be strongly increased in the presence of the lysosomal inhibitor chloroquine. Our data are consistent with the dileucine motifs being involved in destabilization of receptors devoid of associated Jaks as part of a quality control ensuring signaling competence of OSMRs.

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