Cross-regulation of signaling by ITAM-associated receptors.
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.
Ivashkiv
Lionel B
LB
Hospital for Special Surgery, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA. ivashkivl@hss.edu
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D020816:Amino Acid Motifs; D000818:Animals; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D053612:Janus Kinases / Q000276:immunology / Q000502:physiology; D008565:Membrane Proteins / Q000276:immunology; D020239:Receptor Cross-Talk / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D018121:Receptors, Cytokine / Q000276:immunology / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000502:physiology; D050791:STAT Transcription Factors / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D018821:CD18 Antigens; D007135:Immunoglobulin Variable Region; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; D050791:STAT Transcription Factors; C110546:TYROBP protein, human; D051193:Toll-Like Receptors; D053612:Janus Kinases