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Janus kinase (Jak) subcellular localization revisited: the exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak.receptor complex to be equivalent to a receptor tyrosine kinase
Behrmann, Iris; Smyczek, Tanja; Heinrich, Peter C. et al.
2004In Journal of Biological Chemistry, 279 (34), p. 35486-93
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Keywords :
Cell Line; Receptors, Cytokine/metabolism; Receptor Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; Protein-Tyrosine Kinases/metabolism; Protein Binding; Janus Kinase 2; Janus Kinase 1; Humans; Enzyme Activation; Cell Membrane/metabolism; Signal Transduction
Abstract :
[en] The Janus kinases are considered to be cytoplasmic kinases that constitutively associate with the cytoplasmic region of cytokine receptors, and the Janus kinases (Jaks) are crucial for cytokine signal transduction. We investigated Jak1 localization using subcellular fractionation techniques and fluorescence microscopy (immunofluorescence and yellow fluorescent protein-tagged Jaks). In the different experimental approaches we found Jak1 (as well as Jak2 and Tyk2) predominantly located at membranes. In contrast to previous reports we did not observe Jak proteins in significant amounts within the nucleus or in the cytoplasm. The cytoplasmic localization observed for the Jak1 mutant L80A/Y81A, which is unable to associate with cytokine receptors, indicates that Jak1 does not have a strong intrinsic membrane binding potential and that only receptor binding is crucial for the membrane recruitment. Finally we show that Jak1 remains a membrane-localized protein after cytokine stimulation. These data strongly support the hypothesis that cytokine receptor.Janus kinase complexes can be regarded as receptor tyrosine kinases.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
UNILU:UL-ARTICLE-2008-708
Author, co-author :
Behrmann, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Smyczek, Tanja
Heinrich, Peter C.
Schmitz-Van de Leur, Hildegard
Komyod, Waraporn
Giese, Bernd
Muller-Newen, Gerhard
Haan, Serge ;  Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institute for Biochemistry
Haan, Claude ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
yes
Language :
English
Title :
Janus kinase (Jak) subcellular localization revisited: the exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak.receptor complex to be equivalent to a receptor tyrosine kinase
Publication date :
2004
Journal title :
Journal of Biological Chemistry
ISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
279
Issue :
34
Pages :
35486-93
Peer reviewed :
Peer Reviewed verified by ORBi
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