SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells

J Clin Invest. 1999 Jun;103(12):1737-43.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adoptive Transfer
  • Animals
  • Binding Sites / genetics
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology
  • Cell Degranulation / genetics
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Cytokines / metabolism
  • Immunoglobulin E / administration & dosage
  • Immunoglobulin E / physiology
  • Mast Cells / metabolism*
  • Mast Cells / physiology
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Passive Cutaneous Anaphylaxis
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / deficiency*
  • Phosphoproteins / genetics*
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology
  • Receptors, IgE / physiology*
  • Signal Transduction / genetics*


  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Phosphoproteins
  • Receptors, IgE
  • SLP-76 signal Transducing adaptor proteins
  • Immunoglobulin E