TY  - JOUR
A1  - Floss, Doreen M.
A1  - Klöcker, Tobias
A1  - Schröder, Jutta
A1  - Lamertz, Larissa
A1  - Mrotzek, Simone
A1  - Strobl, Birgit
A1  - Hermanns, Heike
A1  - Scheller, Jürgen
T1  - Defining the functional binding sites of interleukin 12 receptor beta 1 and interleukin 23 receptor to Janus kinases
JF  - Molecular Biology of the Cell
N2  - The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor beta 1 (IL-12R beta 1) as one component of their receptor signaling complexes, with IL-12R beta 2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12R beta 1, whereas Jak2 binds to IL-23R and also to IL-12R beta 2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12R beta 1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12R beta 1 and Jak2 by IL-23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable.
KW  - Tyrosine phosphorylation
KW  - Cytokine receptors
KW  - Intracellular domain
KW  - IL-12 family
KW  - Responses
KW  - Signal transduction
KW  - T-cells
KW  - STAT3 activation
KW  - Jak kinases
KW  - Inflammation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188104
VL  - 27
IS  - 14
ER  -