Integrin Signaling in Neutrophils and Macrophages Uses Adaptors Containing Immunoreceptor Tyrosine-based Activation Motifs

Overview

Journal Nat Immunol

Date 2006 Nov 7

PMID 17086186

Citations 200

Authors

Attila Mocsai

Clare L Abram

Zoltan Jakus

Yongmei Hu

Lewis L Lanier

Clifford A Lowell

Affiliations

Soon will be listed here.

Abstract

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.

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