The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module
Engels N, Koenig LM, Schulze W, Radtke D, Vanshylla K, Lutz J, Winkler T, Nitschke L, Wienands J (2014)
Publication Status: Published
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: NATURE PUBLISHING GROUP
Book Volume: 5
DOI: 10.1038/ncomms6456
Abstract
The vigorous response of IgG-switched memory B cells to recurring pathogens involves enhanced signalling from their B-cell antigen receptors (BCRs). However, the molecular signal amplification mechanisms of memory-type BCRs remained unclear. Here, we identify the immunoglobulin tail tyrosine (ITT) motif in the cytoplasmic segments of membrane-bound IgGs (mIgGs) as the principle signal amplification device of memory-type BCRs in higher vertebrates and decipher its signalling microanatomy. We show that different families of protein tyrosine kinases act upstream and downstream of the ITT. Spleen tyrosine kinase (Syk) activity is required for ITT phosphorylation followed by recruitment of the adaptor protein Grb2 into the mIgG-BCR signalosome. Grb2 in turn recruits Bruton's tyrosine kinase (Btk) to amplify BCR-induced Ca2+ mobilization. This molecular interplay of kinases and adaptors increases the antigen sensitivity of memory-type BCRs, which provides a cell-intrinsic trigger mechanism for the rapid reactivation of IgG-switched memory B cells on antigen recall.
Authors with CRIS profile
Daniel Radtke
Professur für Genetik
Thomas Winkler
Professur für Genetik
Lars Nitschke
Professur für Genetik
Involved external institutions
Germany (DE)How to cite
APA:
Engels, N., Koenig, L.M., Schulze, W., Radtke, D., Vanshylla, K., Lutz, J.,... Wienands, J. (2014). The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module. Nature Communications, 5. https://dx.doi.org/10.1038/ncomms6456
MLA:
Engels, Niklas, et al. "The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module." Nature Communications 5 (2014).
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