Die Rolle der Janus-Kinasen-spezifischen Insertion (JSI) in JAK2

The Janus Kinase JAK2 is activated by IL-6-type-cytokines. Furthermore it plays an important role within the signal transduction of other cytokines, as for example erythropoetin and growth factors. In the Institute for Biochemistry of the RWTH Aachen, a structured model of the Kinase domain of JAK 2 was provided. Here, a section of 14 amino acids was identified, which we called the JAK specific insertion (JSI). It was shown that this insertion is specific for Janus Kinases. Based on these results and the work of Saharinen et al. (“Regulation of the JAK2 Tyrosine Kinase by its Kinase like domain, Mol. of Cell. Biol., 2000, 20, 3387”), we proposed that the JAK specific insertion could be responsible for the negative regulation of the Kinase domain of JAK2 by its PseudoKinase domain. We cloned a deletion construct (delta JSI) as well as different point mutations of JAK2 (F1061A, M1062A, M1064A, I1065A). In the further process it showed up that the constructs F1061A, M1064A and I1065A had lost their Kinase activities by the mutations. Interestingly, the M1062A mutant was however more strongly phosphorylated than the wild type JAK2. Besides it was capable to phosphorylate the feedback modulator SOCS3 (suppressor of cytokine signaling 3). By the combination of experimental molecular-biological techniques with theoretical beginnings like the Molecular Modelling we could identify a region within the JAK2, which could be relevant for the regulation of the Kinase domain. Our data point on the fact that the JSI is not involved in the interaction between the JH1 (Janus Kinase-Homology-Domain 1) and the JH2 (Janus Kinase-Homology-Domain 2), but possibly in the substrate connection.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Schmidt, Daniela

Contributors dc:contributor

• Heinrich, Peter C.

• info:eu-repo/classification/ddc/610
• Medizin

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-122800%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:61118