Nature Immunology
- 7, 1326 - 1333 (2006)
Published online: 5 November 2006; | doi:10.1038/ni1407
Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifsAttila Mócsai1, 4, Clare L Abram2, 4, Zoltán Jakus1, Yongmei Hu2, Lewis L Lanier3 & Clifford A Lowell21
Department of Physiology, Semmelweis University School of Medicine, 1088 Budapest, Hungary. 2
Department of Laboratory Medicine, University of California, San Francisco, California, 94143, USA. 3
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, California 94143, USA. 4
These authors contributed equally to this work.
Correspondence should be addressed to Attila Mócsai mocsai@puskin.sote.hu or Clifford A Lowell clifford.lowell@ucsf.edu 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 FcR , were defective in integrin-mediated responses. Activation of the tyrosine kinase Syk by integrins required that DAP12 and FcR 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.
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