Reference : The Jak1 SH2 domain does not fulfill a classical SH2 function in Jak/STAT signaling b...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/785
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
English
Radtke, S.* [> >]
Haan, Serge* mailto [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institute for Biochemistry]
Jörissen, A.* [> >]
Hermanns, H. M. [> >]
Diefenbach, S. [> >]
Smyczek, T. [> >]
Schmitz-Vandeleur, H. [> >]
Heinrich, P. C. [> >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Haan, Claude mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
* These authors have contributed equally to this work.
2005
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
280
27
25760-8
Yes (verified by ORBilu)
International
0021-9258
1083-351X
Baltimore
MD
[en] Amino Acid Sequence ; Mice ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases ; Rats ; Receptors, Cell Surface ; Signal Transduction ; Swine ; Up-Regulation ; Macaca mulatta ; Janus Kinase 1 ; Interleukin-6 ; Animals ; COS Cells ; Cell Line, Tumor ; Cercopithecus aethiops ; Chickens ; Drosophila ; Fibrosarcoma ; Fishes ; Humans ; Interferons ; src Homology Domains
[en] The presence of a Src homology 2 (SH2) domain sequence similarity in the sequence of Janus kinases (Jaks) has been discussed since the first descriptions of these enzymes. We performed an in depth study to determine the function of the Jak1 SH2 domain. We investigated the functionality of the Jak1 SH2 domain by stably reconstituting Jak1-defective human fibrosarcoma cells U4C with endogenous amounts of Jak1 in which the crucial arginine residue Arg466 within the SH2 domain has been replaced by lysine. This mutant still binds to the receptor subunits gp130 and OSMR. Moreover, the SH2 R466K mutation does not affect the subcellular distribution of Jak1 as assessed by cell fractionation and confocal microscopy of cells expressing endogenous levels of non-tagged or a yellow fluorescent protein (YFP)-tagged Jak1-R466K, respectively. Likewise, the signaling capacity of Jak1 was not affected by this point mutation. However, we found that the SH2 domain is structurally important for cytokine receptor binding and surface expression of the OSMR.
http://hdl.handle.net/10993/785
10.1074/jbc.M500822200

There is no file associated with this reference.

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.