Article (Scientific journals)
Jaks and cytokine receptors - an intimate relationship
Haan, Claude; Kreis, Stephanie; Margue, Christiane et al.
2006In Biochemical Pharmacology, 72 (11), p. 1538-46
Peer reviewed


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Keywords :
Animals; Signal Transduction; STAT Transcription Factors; Receptors, Cytokine; Protein Inhibitors of Activated STAT; Phosphorylation; Mice; Janus Kinases; Humans; Cytoskeletal Proteins; src Homology Domains
Abstract :
[en] Most cytokine receptors lack intrinsic kinase activity and many of them signal via Janus kinases (Jaks). These tyrosine kinases are associated with cytokine receptor subunits, they become activated upon receptor triggering and subsequently activate downstream signalling events, e.g. the phosphorylation of STAT transcription factors. The successful interplay between cytokines, their receptors and the connected Jaks not only determines signalling competence but is also vital for intracellular traffic, stability, and fate of the cognate receptors. Here, we will discuss underlying mechanisms as well as some structural features with a focus on Jak1 and two of the signal transducing receptor subunits of interleukin (IL)-6 type cytokines, gp130 and OSMR. Regions that are critically involved in Jak-binding have been identified for many cytokine receptor subunits. In most cases the membrane-proximal parts comprising the box1 and box2 regions within the receptor are involved in this association while, within Jaks, the N-terminal FERM domain, possibly together with the SH2-like domain, are pivotal for binding to the relevant receptors. The exclusive membrane localisation of Jaks depends on their ability to associate with cytokine receptors. For gp130 and Jak1, it was shown that the cytokine receptor/Jak complex can be regarded as a receptor tyrosine kinase since both molecules have the same diffusion dynamics and are virtually undissociable. Furthermore, Jaks take an active role in the regulation of the surface expression of at least some cytokine receptors, including the OSMR and this may provide a quality control mechanism ensuring that only signalling-competent receptors (i.e. those with an associated Jak) would be enriched at the cell surface.
Research center :
University of Luxembourg
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
Author, co-author :
Haan, Claude ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Kreis, Stephanie ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Margue, Christiane  
Behrmann, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
Language :
Title :
Jaks and cytokine receptors - an intimate relationship
Publication date :
November 2006
Journal title :
Biochemical Pharmacology
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer reviewed
Focus Area :
Systems Biomedicine
Funders :
DFG - Deutsche Forschungsgemeinschaft [DE]
Unilu - University of Luxembourg [LU]
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since 19 August 2013


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