Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs

Nat Immunol. 2006 Dec;7(12):1326-33. doi: 10.1038/ni1407. Epub 2006 Nov 5.


At sites of inflammation, ligation of leukocyte integrins is critical for the activation of cellular effector functions required for host defense. However, the signaling pathways linking integrin ligation to cellular responses are poorly understood. Here we show that integrin signaling in neutrophils and macrophages requires adaptors containing immunoreceptor tyrosine-based activation motifs (ITAMs). Neutrophils and macrophages lacking two ITAM-containing adaptor proteins, DAP12 and FcRgamma, were defective in integrin-mediated responses. Activation of the tyrosine kinase Syk by integrins required that DAP12 and FcRgamma were first phosphorylated by Src family kinases. Retroviral transduction of neutrophils and macrophages with wild-type and mutant Syk or DAP12 demonstrated that the Src homology 2 domains of Syk and the ITAM of DAP12 were required for integrin signaling. Our data show that integrin signaling for the activation of cellular responses in neutrophils and macrophages proceeds by an immunoreceptor-like mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Motifs / immunology
  • Animals
  • Flow Cytometry
  • Immunoblotting
  • Integrins / immunology
  • Integrins / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / immunology*
  • Tyrosine / metabolism


  • Adaptor Proteins, Signal Transducing
  • Integrins
  • Receptors, Immunologic
  • Tyrosine
  • Protein-Tyrosine Kinases