PMID- 10377180 OWN - NLM STAT- MEDLINE DCOM- 19990707 LR - 20181201 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 103 IP - 12 DP - 1999 Jun TI - SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells. PG - 1737-43 AB - 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. FAU - Pivniouk, V I AU - Pivniouk VI AD - Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Martin, T R AU - Martin TR FAU - Lu-Kuo, J M AU - Lu-Kuo JM FAU - Katz, H R AU - Katz HR FAU - Oettgen, H C AU - Oettgen HC FAU - Geha, R S AU - Geha RS LA - eng GR - P01 AI035714/AI/NIAID NIH HHS/United States GR - R01 AI041144/AI/NIAID NIH HHS/United States GR - AI-35714/AI/NIAID NIH HHS/United States GR - AI-41144/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cytokines) RN - 0 (Phosphoproteins) RN - 0 (Receptors, IgE) RN - 0 (SLP-76 signal Transducing adaptor proteins) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Adoptive Transfer MH - Animals MH - Binding Sites/genetics MH - Bone Marrow Cells/metabolism/physiology MH - Cell Degranulation/genetics MH - Cell Differentiation/genetics MH - Cells, Cultured MH - Cytokines/metabolism MH - Immunoglobulin E/administration & dosage/physiology MH - Mast Cells/*metabolism/physiology MH - Mice MH - Mice, Inbred Strains MH - Mice, Knockout MH - Passive Cutaneous Anaphylaxis MH - Phosphoproteins/biosynthesis/*deficiency/*genetics MH - Receptors, IgE/genetics/immunology/*physiology MH - Signal Transduction/*genetics PMC - PMC408386 EDAT- 1999/06/22 00:00 MHDA- 1999/06/22 00:01 PMCR- 1999/06/15 CRDT- 1999/06/22 00:00 PHST- 1999/06/22 00:00 [pubmed] PHST- 1999/06/22 00:01 [medline] PHST- 1999/06/22 00:00 [entrez] PHST- 1999/06/15 00:00 [pmc-release] AID - 06338 [pii] PST - ppublish SO - J Clin Invest. 1999 Jun;103(12):1737-43.