2026-04-27T12:29:20Zhttps://uvadoc.uva.es/oai/request

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

WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells Kettner, Alexander Kumar, Lalit Antón, Inés María Sasahara, Yoji Pivniouk, Vadim Falet, Hervé Hartwig, John H. Geha, Raif S. Fuente García, Miguel Ángel de la Síndrome de Wiskott-Aldrich Producción Científica 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. 2015-03-26T12:57:47Z 2015-03-26T12:57:47Z 2004 info:eu-repo/semantics/article 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 eng https://rupress.org/jem/article/199/3/357/40031/WIP-Regulates-Signaling-via-the-High-Affinity info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/3.0/ Attribution-NonCommercial-NoDerivatives 3.0 International Rockefeller University Press SI