title: Cbl family proteins: balancing FcεRI-mediated mast cell and basophil activation.
abstract: The binding of IgE to high-affinity IgE receptors (FcεRI) expressed on the surface of mast cells and basophils initiates a cascade of signaling events that results in the release of a wide array of proinflammatory mediators. In order to limit the intensity and duration of cell activation, FcεRI aggregation has been understood to additionally generate negative signals through the coordinated action of adapters, phosphatases, and ubiquitin ligases. Among them, Cbl family proteins negatively regulate FcεRI-mediated signals mainly by promoting ubiquitination of the activated receptor subunits and associated protein tyrosine kinases. Notably, FcεRI ubiquitination has become recognized as an important signal for the internalization and delivery of engaged receptor complexes to lysosomes for degradation. The surface expression of activated FcεRI complexes is further downregulated through a pathway that is functionally separable from Cbl ligase activity and is dependent on the interaction of Cbl proteins with adapters involved in clathrin-dependent endocytosis. In this article, we review recent advances in our understanding of the molecular mechanisms through which Cbl proteins negatively regulate FcεRI-mediated mast cell and basophil functions.
authors: Department of Molecular Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Rome, Italy.
authors: Francesca
authors: F
authors: Gasparrini
authors: Rosa
authors: R
authors: Molfetta
authors: Angela
authors: A
authors: Santoni
authors: Rossella
authors: R
authors: Paolini
mesh_terms: D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D017455:Receptors, IgE; D025801:Ubiquitin; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human