Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcɛRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcɛRI-mediated signaling than LAT−/− mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcɛRI-mediated signaling.
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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