title: A role for prohibitin in mast cell activation: location matters.
abstract: Prohibitin 1 (PHB1) and PHB2 are evolutionarily conserved, ubiquitously expressed, pleotropic proteins that control various fundamental cellular processes, including proliferation, migration, metabolism, and death. Studies have unveiled a crucial role for plasma membrane-associated PHBs in regulating tumor metastasis, viral entry, and immune cell activation. A study now identifies a role for PHB1 in the activation of mast cells and allergic reactions mediated by immunoglobulin E (IgE). PHB1 was primarily localized in mast cell granules; however, in response to stimulation with antigen, PHB1 translocated to plasma membrane lipid rafts to form a ternary complex with the high-affinity IgE receptor FcεRIγ and the nonreceptor tyrosine kinase Syk. Syk became activated, which led to the activation of downstream signaling that stimulated mast cell degranulation and the secretion of cytokines. PHB1 was phosphorylated by the Src family tyrosine kinase Lyn, and palmitoylation of PHB1 was required for its association with the plasma membrane. These observations unveil a previously uncharacterized facet of prohibitin biology and shed further light on the proximal events that drive the activation of FcεRI by IgE in mast cells during allergic reactions.
authors.affiliation: 1Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kitaku, Kyoto 603-8555, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yurugi
authors.forename: Krishnaraj
authors.initials: K
authors.lastname: Rajalingam
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D000091402:Prohibitins; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase
chemical_list: D000941:Antigens; C543372:FcepsilonRI gamma-chain, human; D047908:Intracellular Signaling Peptides and Proteins; C000717328:PHB protein, human; C000717331:PHB2 protein, human; D000091402:Prohibitins; D017455:Receptors, IgE; D012097:Repressor Proteins; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase