Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Novel Role of Janus Kinase 1 in the Regulation of Oncostatin M
Receptor Surface Expression*
Simone
Radtke,
Heike M.
Hermanns,
Claude
Haan,
Hildegard
Schmitz-Van de Leur,
Hugues
Gascan,
Peter C.
Heinrich, and
Iris
Behrmann§
From the Institut für Biochemie, Universitätsklinikum
der Rheinisch-Westfälischen Technischen Hochschule Aachen,
Pauwelsstr. 30, 52074 Aachen, Germany and INSERM E 9928, Centre hospitalier universitaire Angers, Batiment Monteclair, 4 Rue
Larrey, 49033 Angers, France
The oncostatin M receptor (OSMR) is part of a
heterodimeric receptor complex that mediates signal transduction of the
pleiotropiccytokine OSM via a signaling pathway involving Janus
kinases (Jaks)and transcription factors of the signal transducers and
activatorsof transcription (STAT) family. Upon heterologous expression
ofthe OSMR in several cell lines, we observed that its surface
expressionwas significantly enhanced by coexpression of the Janus
kinasesJak1, Jak2, and Tyk2 but not Jak3. Chimeric receptors
consistingof the extracellular region of the interleukin-5
receptor chainand the transmembrane and intracellular part of the
OSMR weresimilarly up-regulated on the plasma membrane when Jak1 was
coexpressed.The overall expression level of these constructs did not
changesignificantly, but Jak1 coexpression increased the amount of
endoglycosidaseH-resistant, fully processed OSMR chimeras.
Using mutated receptorand Jak1 constructs, we were able to demonstrate
that associationof Jak1 with the membrane proximal region of the
receptor, butnot its kinase activity, is necessary for this effect.
Moreover,deletion of the OSMR box1/2 region also resulted in an
improvedsurface expression indicating that this region may contain a
signalpreventing efficient receptor surface expression in the absenceof associated Jaks. Finally we demonstrate that in Jak1-deficientcells, the endogenous OSMR is significantly down-regulated, aneffect
that can be reversed by transient expression of Jak1 inthesecells.
Th17 Cells in Multiple Sclerosis Express Higher Levels of JAK2, Which Increases Their Surface Expression of IFN-{gamma}R2.
L. Conti, R. De Palma, S. Rolla, D. Boselli, G. Rodolico, S. Kaur, O. Silvennoinen, E. Niccolai, A. Amedei, F. Ivaldi, et al. (2012)
J. Immunol.
188, 1011-1018
|Abstract »|Full Text »|PDF »
RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding.
J. Wauman, L. De Ceuninck, N. Vanderroost, S. Lievens, and J. Tavernier (2011)
J. Cell Sci.
124, 921-932
|Abstract »|Full Text »|PDF »
Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor.
C. Pecquet, J. Staerk, R. Chaligne, V. Goss, K. A. Lee, X. Zhang, J. Rush, J. Van Hees, H. A. Poirel, J.-M. Scheiff, et al. (2010)
Blood
115, 1037-1048
|Abstract »|Full Text »|PDF »
Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation.
C. Hintzen, C. Evers, B. E. Lippok, R. Volkmer, P. C. Heinrich, S. Radtke, and H. M. Hermanns (2008)
J. Biol. Chem.
283, 19465-19477
|Abstract »|Full Text »|PDF »
Basal Ubiquitin-independent Internalization of Interferon {alpha} Receptor Is Prevented by Tyk2-mediated Masking of a Linear Endocytic Motif.
K. G. S. Kumar, B. Varghese, A. Banerjee, D. P. Baker, S. N. Constantinescu, S. Pellegrini, and S. Y. Fuchs (2008)
J. Biol. Chem.
283, 18566-18572
|Abstract »|Full Text »|PDF »
Substitution of Pseudokinase Domain Residue Val-617 by Large Non-polar Amino Acids Causes Activation of JAK2.
A. Dusa, J. Staerk, J. Elliott, C. Pecquet, H. A. Poirel, J. A. Johnston, and S. N. Constantinescu (2008)
J. Biol. Chem.
283, 12941-12948
|Abstract »|Full Text »|PDF »
Dual Role of the Jak1 FERM and Kinase Domains in Cytokine Receptor Binding and in Stimulation-Dependent Jak Activation.
S. Haan, C. Margue, A. Engrand, C. Rolvering, H. Schmitz-Van de Leur, P. C. Heinrich, I. Behrmann, and C. Haan (2008)
J. Immunol.
180, 998-1007
|Abstract »|Full Text »|PDF »
Endoplasmic Reticulum-Associated Degradation of Growth Hormone Receptor in Janus Kinase 2-Deficient Cells.
K. Loesch, L. Deng, X. Wang, K. He, J. Jiang, and S. J. Frank (2007)
Endocrinology
148, 5955-5965
|Abstract »|Full Text »|PDF »
In the absence of IGF-1 signaling, IFN-{gamma} suppresses human malignant T-cell growth.
L. Conti, G. Regis, A. Longo, P. Bernabei, R. Chiarle, M. Giovarelli, and F. Novelli (2007)
Blood
109, 2496-2504
|Abstract »|Full Text »|PDF »
Interleukin-31 and Oncostatin-M Mediate Distinct Signaling Reactions and Response Patterns in Lung Epithelial Cells.
S. Chattopadhyay, E. Tracy, P. Liang, O. Robledo, S. Rose-John, and H. Baumann (2007)
J. Biol. Chem.
282, 3014-3026
|Abstract »|Full Text »|PDF »
The Membrane-proximal Region of the Thrombopoietin Receptor Confers Its High Surface Expression by JAK2-dependent and -independent Mechanisms.
W. Tong, R. Sulahian, A. W. Gross, N. Hendon, H. F. Lodish, and L. J.-s. Huang (2006)
J. Biol. Chem.
281, 38930-38940
|Abstract »|Full Text »|PDF »
K. Loesch, L. Deng, J. W. Cowan, X. Wang, K. He, J. Jiang, R. A. Black, and S. J. Frank (2006)
Endocrinology
147, 2839-2849
|Abstract »|Full Text »|PDF »
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.
S. Radtke, A. Jorissen, H. S.-V. de Leur, P. C. Heinrich, and I. Behrmann (2006)
J. Biol. Chem.
281, 4024-4034
|Abstract »|Full Text »|PDF »
Janus Kinase 2 Enhances the Stability of the Mature Growth Hormone Receptor.
K. He, K. Loesch, J. W. Cowan, X. Li, L. Deng, X. Wang, J. Jiang, and S. J. Frank (2005)
Endocrinology
146, 4755-4765
|Abstract »|Full Text »|PDF »
Mechanisms of SOCS3 Phosphorylation upon Interleukin-6 Stimulation: CONTRIBUTIONS OF Src- AND RECEPTOR-TYROSINE KINASES.
U. Sommer, C. Schmid, R. M. Sobota, U. Lehmann, N. J. Stevenson, J. A. Johnston, F. Schaper, P. C. Heinrich, and S. Haan (2005)
J. Biol. Chem.
280, 31478-31488
|Abstract »|Full Text »|PDF »
Janus Kinases Affect Thrombopoietin Receptor Cell Surface Localization and Stability.
Y. Royer, J. Staerk, M. Costuleanu, P. J. Courtoy, and S. N. Constantinescu (2005)
J. Biol. Chem.
280, 27251-27261
|Abstract »|Full Text »|PDF »
IL-1{beta} Induces IL-6 Expression in Human Orbital Fibroblasts: Identification of an Anatomic-Site Specific Phenotypic Attribute Relevant to Thyroid-Associated Ophthalmopathy.
The Jak1 SH2 Domain Does Not Fulfill a Classical SH2 Function in Jak/STAT Signaling but Plays a Structural Role for Receptor Interaction and Up-regulation of Receptor Surface Expression.
S. Radtke, S. Haan, A. Jorissen, H. M. Hermanns, S. Diefenbach, T. Smyczek, H. Schmitz-VandeLeur, P. C. Heinrich, I. Behrmann, and C. Haan (2005)
J. Biol. Chem.
280, 25760-25768
|Abstract »|Full Text »|PDF »
Jamip1 (Marlin-1) Defines a Family of Proteins Interacting with Janus Kinases and Microtubules.
C. Steindler, Z. Li, M. Algarte, A. Alcover, V. Libri, J. Ragimbeau, and S. Pellegrini (2004)
J. Biol. Chem.
279, 43168-43177
|Abstract »|Full Text »|PDF »
Janus Kinase (Jak) Subcellular Localization Revisited: THE EXCLUSIVE MEMBRANE LOCALIZATION OF ENDOGENOUS JANUS KINASE 1 BY CYTOKINE RECEPTOR INTERACTION UNCOVERS THE Jak{middle dot}RECEPTOR COMPLEX TO BE EQUIVALENT TO A RECEPTOR TYROSINE KINASE.
I. Behrmann, T. Smyczek, P. C. Heinrich, H. Schmitz-Van de Leur, W. Komyod, B. Giese, G. Muller-Newen, S. Haan, and C. Haan (2004)
J. Biol. Chem.
279, 35486-35493
|Abstract »|Full Text »|PDF »
Janus Kinase 2 Determinants for Growth Hormone Receptor Association, Surface Assembly, and Signaling.
K. He, X. Wang, J. Jiang, R. Guan, K. E. Bernstein, P. P. Sayeski, and S. J. Frank (2003)
Mol. Endocrinol.
17, 2211-2227
|Abstract »|Full Text »|PDF »
Long Term Association of the Cytokine Receptor gp130 and the Janus Kinase Jak1 Revealed by FRAP Analysis.
B. Giese, C.-K. Au-Yeung, A. Herrmann, S. Diefenbach, C. Haan, A. Kuster, S. B. Wortmann, C. Roderburg, P. C. Heinrich, I. Behrmann, et al. (2003)
J. Biol. Chem.
278, 39205-39213
|Abstract »|Full Text »|PDF »
The Pseudokinase Domain Is Required for Suppression of Basal Activity of Jak2 and Jak3 Tyrosine Kinases and for Cytokine-inducible Activation of Signal Transduction.
,
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.
