| Reference : Mapping of a region within the N terminus of Jak1 involved in cytokine receptor inter... |
| Scientific journals : Article | |||
| Life sciences : Biochemistry, biophysics & molecular biology | |||
| http://hdl.handle.net/10993/6245 | |||
| Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction | |
| English | |
Haan, Claude  [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >] | |
| Isharc, H. [> >] | |
| Hermanns, H. M. [> >] | |
| Schmitz-Van De Leur, H. [> >] | |
| Kerr, I. M. [> >] | |
| Heinrich, P. C. [> >] | |
| Grötzinger, J. [> >] | |
| Behrmann, Iris [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >] | |
| 2001 | |
| Journal of Biological Chemistry | |
| American Society for Biochemistry and Molecular Biology | |
| 276 | |
| 40 | |
| 37451-8 | |
| Yes (verified by ORBilu) | |
| International | |
| 0021-9258 | |
| 1083-351X | |
| Baltimore | |
| MD | |
| [en] Tyrosine ; Interferons ; Cytokine Receptor gp130 ; COS Cells ; Binding Sites ; Antigens, CD ; Animals ; Amino Acid Substitution ; Amino Acid Sequence ; Janus Kinase 1 ; Membrane Glycoproteins ; Signal Transduction ; Sequence Homology, Amino Acid ; Receptors, Cytokine ; Protein-Tyrosine Kinases ; Protein Structure, Tertiary ; Mutagenesis, Site-Directed ; Molecular Sequence Data ; Models, Molecular ; Alanine | |
| [en] Janus kinase 1 (Jak1) is a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors. Here we show that the in vitro translated N-terminal domains of Jak1 are sufficient for binding to a biotinylated peptide comprising the membrane-proximal 73 amino acids of gp130, the signal-transducing receptor chain of interleukin-6-type cytokines. By the fold recognition approach amino acid residues 36-112 of Jak1 were predicted to adopt a beta-grasp fold, and a structural model was built using ubiquitin as a template. Substitution of Tyr(107) to alanine, a residue conserved among Jaks and involved in hydrophobic core interactions of the proposed beta-grasp domain, abrogated binding of full-length Jak1 to gp130 in COS-7 transfectants. By further mutagenesis we identified the loop 4 region of the Jak1 beta-grasp domain as essential for gp130 association and gp130-mediated signal transduction. In Jak1-deficient U4C cells reconstituted with the loop 4 Jak1 mutants L80A/Y81A and Delta(Tyr(81)-Ser(84)), the interferon-gamma, interferon-alpha, and interleukin-6 responses were similarly impaired. Thus, loop 4 of the beta-grasp domain plays a role in the association of Jak1 with both class I and II cytokine receptors. Taken together the structural model and the mutagenesis data provide further insight into the interaction of Janus kinases with cytokine receptors. | |
| http://hdl.handle.net/10993/6245 | |
| 10.1074/jbc.M106135200 |
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