Cross-regulation of signaling by ITAM-associated receptors

LB Ivashkiv - Nature immunology, 2009 - nature.com
LB Ivashkiv
Nature immunology, 2009nature.com
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 …
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 β2 integrins that are coupled to the ITAM-containing adaptors DAP12 and FcRγ. 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.
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