title: SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells.
abstract: SLP-76 is an adapter protein expressed in T cells and myeloid cells that is a substrate for ZAP-70 and Syk. SLP-76-deficient mice exhibit a profound block in T-cell development. We found that although SLP-76 is expressed in mouse mast cells, SLP-76(-/-) mice have normal numbers of mast cells in their skin and bronchi. SLP-76(-/-) mice are resistant to IgE-mediated passive anaphylaxis. SLP-76(-/-) mice sensitized with IgE anti-dinitrophenyl (DNP) and then challenged with DNP-HSA developed only mild and transient tachycardia, failed to increase their plasma histamine level, and all survived the antigen challenge. Bone marrow-derived mast cells (BMMCs) from SLP76(-/-) mice failed to release beta-hexosaminidase and to secrete IL-6 after FcepsilonRI cross-linking. Tyrosine phosphorylation of phospholipase C-gamma1 (but not of Syk) and calcium mobilization in response to IgE cross-linking were reduced in SLP-76-deficient BMMCs. These results suggest that SLP-76 plays an important role in FcepsilonRI-mediated signaling in mast cells.
authors.affiliation: Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: V I
authors.initials: VI
authors.lastname: Pivniouk
authors.forename: T R
authors.initials: TR
authors.lastname: Martin
authors.forename: J M
authors.initials: JM
authors.lastname: Lu-Kuo
authors.forename: H R
authors.initials: HR
authors.lastname: Katz
authors.forename: H C
authors.initials: HC
authors.lastname: Oettgen
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019264:Adoptive Transfer; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D015550:Cell Degranulation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007073:Immunoglobulin E / Q000008:administration & dosage / Q000502:physiology; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis; D010750:Phosphoproteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D010750:Phosphoproteins; D017455:Receptors, IgE; C092947:SLP-76 signal Transducing adaptor proteins; D007073:Immunoglobulin E