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LAB: A new membrane-associated adaptor molecule in B cell activation

Abstract

The adaptor molecule, linker for activation of T cells (LAT), is essential in T cell activation and development; a similar molecule in B cells has not yet been identified. Here, we report the identification of a new adaptor protein, linker for activation of B cells (LAB). Like LAT, LAB was localized to lipid rafts. Upon activation via the B cell receptor (BCR), LAB was phosphorylated and interacted with the adaptor protein Grb2. Decreased LAB expression led to a reduction in BCR-mediated calcium flux and Erk activation. LAB rescued thymocyte development but not normal T cell activation in LAT−/− mice. Our data suggest that LAB links BCR engagement to downstream signaling pathways.

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Figure 1: LAB sequence comparison.
Figure 2: LAB expression in B cells.
Figure 3: Localization of LAB in lipid rafts of the B cell membrane.
Figure 4: Tyrosine phosphorylation of LAB.
Figure 5: LAB association with Grb2, PLC-γ1 and PLC-γ2.
Figure 6: Decreased calcium flux and Erk activation with downregulated LAB protein expression.
Figure 7: LAB compensation for LAT in thymocyte development.
Figure 8: LAB function in T cell activation.

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Acknowledgements

We thank the Duke University Cancer Center Flow Cytometry and Sequencing facilities. This work is supported by National Institutes of Health Grant 1R01 AI48674-01.

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Correspondence to Weiguo Zhang.

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Janssen, E., Zhu, M., Zhang, W. et al. LAB: A new membrane-associated adaptor molecule in B cell activation. Nat Immunol 4, 117–123 (2003). https://doi.org/10.1038/ni882

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