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

Vadim I. Pivniouk, Thomas R. Martin, Jennifer M. Lu-Kuo, Howard R. Katz, Hans C. Oettgen, Raif S. Geha

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


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 β-hexosaminidase and to secrete IL-6 after FcεRI cross-linking. Tyrosine phosphorylation of phospholipase C-γ1 (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 FcεRI-mediated signaling in mast cells.

Original languageEnglish (US)
Pages (from-to)1737-1743
Number of pages7
JournalJournal of Clinical Investigation
Issue number12
StatePublished - Jun 1999

ASJC Scopus subject areas

  • General Medicine


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