Bruton's tyrosine kinase (Btk) represents an important signaling element downstream of ITAM-containing receptors, e.g. FcεR1 and BCR. Btk is part of the calcium signalosome and thus, critically involved in intracellular calcium mobilization. Loss of Btk or expression of mutant forms results in severe disease phenotypes, X-linked agammaglobulinemia (XLA) and Xid in humans and mice, respectively. Previously, roles for Btk in TLR-mediated signal transduction have been found in monocytes/macrophages. In the present study we show that Btk deficiency moderately enhances or has no influence on the LPS- or lipopeptide-induced secretion of IL-6 and TNF-α from murine bone marrow-derived mast cells (BMMCs). Furthermore, activation of p38 kinase, which is required for cytokine production, is comparable in WT and Btk-/- BMMCs. Moreover, stability of the adaptor protein Mal as well as LPS-induced H2O2production does not vary between WT and Btk-/- cells. Interestingly, PKC-β deficiency, which results in a Xid-like phenotype as well, has also no negative effect on LPS-induced cytokine secretion, suggesting that proteins of the calcium signalosome are not involved in TLR-mediated BMMC activation. In conclusion, the study reveals that Btk is dispensable for TLR signaling and function in murine BMMCs.

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doi.org/10.1016/j.cellsig.2008.09.010, hdl.handle.net/1765/25034
Cellular Signalling
Erasmus MC: University Medical Center Rotterdam

Zorn, C., Keck, S., Hendriks, R., Leitges, M., Freudenberg, M., & Huber, M. (2009). Bruton's tyrosine kinase is dispensable for the Toll-like receptor-mediated activation of mast cells. Cellular Signalling, 21(1), 79–86. doi:10.1016/j.cellsig.2008.09.010