The receptor tyrosine kinase c-Kit controls IL-33 receptor signaling in mast cells

Drube, Sebastian and Heink, Sylvia and Walter, Sabine and Löhn, Tobias and Grusser, Mandy and Gerbaulet, Alexander and Berod, Luciana and Schons, Julia and Dudeck, Anne and Freitag, Jenny and Grotha, Stefan and Reich, Daniela and Rudeschko, Olga and Norgauer, Johannes and Hartmann, Karin and Roers, Axel and Kamradt, Thomas. (2010) The receptor tyrosine kinase c-Kit controls IL-33 receptor signaling in mast cells. Blood, 115 (19). pp. 3899-3906.

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Official URL: https://edoc.unibas.ch/70820/

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Members of the Toll/interleukin-1 receptor (TIR) family are of importance for host defense and inflammation. Here we report that the TIR-family member interleukin-33R (IL-33R) cross-activates the receptor tyrosine kinase c-Kit in human and murine mast cells. The IL-33R-induced activation of signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase B (PKB), and Jun NH(2)-terminal kinase 1 (JNK1) depends on c-Kit and is required to elicit optimal effector functions. Costimulation with the c-Kit ligand stem cell factor (SCF) is necessary for IL-33-induced cytokine production in primary mast cells. The structural basis for this cross-activation is the complex formation between c-Kit, IL-33R, and IL-1R accessory protein (IL-1RAcP). We found that c-Kit and IL-1RAcP interact constitutively and that IL-33R joins this complex upon ligand binding. Our findings support a model in which signals from seemingly disparate receptors are integrated for full cellular responses.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Hematology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Nov 2020 16:18
Deposited On:10 Nov 2020 16:18

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