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Publication : Nonredundant roles of Src-family kinases and Syk in the initiation of B-cell antigen receptor signaling.

First Author  Stepanek O Year  2013
Journal  J Immunol Volume  190
Issue  4 Pages  1807-18
PubMed ID  23335753 Mgi Jnum  J:193494
Mgi Id  MGI:5468618 Doi  10.4049/jimmunol.1202401
Citation  Stepanek O, et al. (2013) Nonredundant roles of SRC-family kinases and syk in the initiation of B-cell antigen receptor signaling. J Immunol 190(4):1807-18
abstractText  When a BCR on a mature B cell is engaged by its ligand, the cell becomes activated, and the Ab-mediated immune response can be triggered. The initiation of BCR signaling is orchestrated by kinases of the Src and Syk families. However, the proximal BCR-induced phosphorylation remains incompletely understood. According to a model of sequential activation of kinases, Syk acts downstream of Src family kinases (SFKs). In addition, signaling independent of SFKs and initiated by Syk has been proposed. Both hypotheses lack sufficient evidence from relevant B cell models, mainly because of the redundancy of Src family members and the importance of BCR signaling for B cell development. We addressed this issue by analyzing controlled BCR triggering ex vivo on primary murine B cells and on murine and chicken B cell lines. Chemical and Csk-based genetic inhibitor treatments revealed that SFKs are required for signal initiation and Syk activation. In addition, ligand and anti-BCR Ab-induced signaling differ in their sensitivity to the inhibition of SFKs.
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