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Nat Immunol. 2009 Apr;10(4):340-7. doi: 10.1038/ni.1706. Epub 2009 Mar 19.

Cross-regulation of signaling by ITAM-associated receptors.

Author information

  • Hospital for Special Surgery, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA. ivashkivl@hss.edu

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 beta2 integrins that are coupled to the ITAM-containing adaptors DAP12 and FcRgamma. 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.

PMID:
19295630
[PubMed - indexed for MEDLINE]
PMCID:
PMC2753670
Free PMC Article

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