Novel role of Janus kinase 1 in the regulation of oncostatin M receptor surface expression.
The oncostatin M receptor (OSMR) is part of a heterodimeric receptor complex that mediates signal transduction of the pleiotropic cytokine OSM via a signaling pathway involving Janus kinases (Jaks) and transcription factors of the signal transducers and activators of transcription (STAT) family. Upon heterologous expression of the OSMR in several cell lines, we observed that its surface expression was significantly enhanced by coexpression of the Janus kinases Jak1, Jak2, and Tyk2 but not Jak3. Chimeric receptors consisting of the extracellular region of the interleukin-5 receptor beta chain and the transmembrane and intracellular part of the OSMR were similarly up-regulated on the plasma membrane when Jak1 was coexpressed. The overall expression level of these constructs did not change significantly, but Jak1 coexpression increased the amount of endoglycosidase H-resistant, fully processed OSMR chimeras. Using mutated receptor and Jak1 constructs, we were able to demonstrate that association of Jak1 with the membrane proximal region of the receptor, but not its kinase activity, is necessary for this effect. Moreover, deletion of the OSMR box1/2 region also resulted in an improved surface expression indicating that this region may contain a signal preventing efficient receptor surface expression in the absence of associated Jaks. Finally we demonstrate that in Jak1-deficient cells, the endogenous OSMR is significantly down-regulated, an effect that can be reversed by transient expression of Jak1 in these cells.
Radtke
Simone
S
Institut für Biochemie, Universitätsklinikum der Rheinisch-Westfälischen Technischen Hochschule Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
Hermanns
Heike M
HM
Haan
Claude
C
Schmitz-Van De Leur
Hildegard
H
Gascan
Hugues
H
Heinrich
Peter C
PC
Behrmann
Iris
I
D000818:Animals; D019556:COS Cells; D006367:HeLa Cells; D006801:Humans; D053613:Janus Kinase 1; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism*; D053677:Receptors, Oncostatin M; D015854:Up-Regulation
D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1