| First Author | Drube S | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 19 | Pages | 3899-906 |
| PubMed ID | 20200353 | Mgi Jnum | J:160247 |
| Mgi Id | MGI:4453925 | Doi | 10.1182/blood-2009-10-247411 |
| Citation | Drube S, et al. (2010) The receptor tyrosine kinase c-Kit controls IL-33 receptor signaling in mast cells. Blood 115(19):3899-906 |
| abstractText | 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. |
