Sci. Signal., 10 September 2013
How to Prohibit Mast Cell ActivationMast cells are the major effector cells of the allergic response. Binding of antigen to immunoglobulin E (IgE) molecules bound to the cell-surface, high-affinity IgE receptor FcRI results in receptor clustering, mast cell activation, and degranulation, resulting in the release of factors that mediate the allergic response. Phosphorylation and activation of the Src family kinases Lyn and Syk are critical for mast cell activation. Kim et al. found that the scaffold protein prohibitin (PHB), which mediates functions such as mitochondrial biogenesis and transcriptional regulation (see commentary by Yurugi and Rajalingam), was abundant in intracellular granules in mouse mast cells. Stimulation of mast cells with antigen resulted in the translocation of PHB to plasma membrane lipid rafts, which was required for the association of FcRI with Syk, the activation of Syk, and degranulation. Knockdown of PHB in mice inhibited mast cell activation and anaphylaxis, suggesting that targeting PHB therapeutically may reduce allergic responses.
Citation: D. K. Kim, H. S. Kim, A.-R. Kim, G. H. Jang, H. W. Kim, Y. H. Park, B. Kim, Y. M. Park, M. A. Beaven, Y. M. Kim, W. S. Choi, The Scaffold Protein Prohibitin Is Required for Antigen-Stimulated Signaling in Mast Cells. Sci. Signal. 6, ra80 (2013).
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