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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
Radtke, S.; Haan, Serge; Jörissen, A. et al.
2005In Journal of Biological Chemistry, 280 (27), p. 25760-8
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Keywords :
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
Abstract :
[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cells U4C with endogenous amounts of Jak1 in which the crucial arginine residue Arg466 within the SH2 domain has been replaced by lysine.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.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
UNILU:UL-ARTICLE-2008-706
Author, co-author :
Radtke, S. 
Haan, Serge  ;  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 ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Haan, Claude ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
 These authors have contributed equally to this work.
External co-authors :
yes
Language :
English
Title :
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
Publication date :
2005
Journal title :
Journal of Biological Chemistry
ISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
280
Issue :
27
Pages :
25760-8
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 26 April 2013

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