Review abstract
Nature Immunology 10, 340 - 347 (2009)
Published online: 19 March 2009 | doi:10.1038/ni.1706
Cross-regulation of signaling by ITAM-associated receptors
Lionel B Ivashkiv1
Abstract
An important function of receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs) is to regulate signaling by heterologous receptors. This review describes mechanisms by which ITAM-associated receptors modulate signaling by Toll-like receptors (TLRs), tumor necrosis factor receptor family members and cytokine receptors that use the Jak–STAT signaling pathway, and the biological importance of this signal transduction cross-talk. ITAM-mediated cross-regulation can either augment or dampen signaling by other receptors. Conversely, TLRs and cytokines modulate ITAM-mediated signaling, by means including activation of 
2 integrins that are coupled to the ITAM-containing adaptors DAP12 and FcR
. Integration of ITAM signaling into signaling networks through cross-talk with other signal transduction pathways results in tight regulation and fine tuning of cellular responses to various extracellular stimuli and contributes to induction of specific activation and differentiation pathways.
- Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.
Correspondence to: Lionel B Ivashkiv1 e-mail: ivashkivl@hss.edu
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