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oai:uvadoc.uva.es:10324/101252025-05-14T09:08:46Zcom_10324_1133com_10324_931com_10324_894col_10324_1209

00925njm 22002777a 4500 dc Kettner, Alexander author Kumar, Lalit author Antón, Inés María author Sasahara, Yoji author Pivniouk, Vadim author Falet, Hervé author Hartwig, John H. author Geha, Raif S. author Fuente García, Miguel Ángel de la author 2004 Wiskott-Aldrich syndrome protein-interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcepsilonRI) in mast cells. WIP-deficient bone marrow-derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcepsilonRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcepsilonRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement. Journal of Experimental Medicine, 2004, vol. 199, n. 3. p. 357-368 0022-1007 http://uvadoc.uva.es/handle/10324/10125 10.1084/jem.20030652 357 3 368 Journal of Experimental Medicine 199 Síndrome de Wiskott-Aldrich WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells