A signal-switch hypothesis for cross-regulation of cytokine and TLR signalling pathways.
The importance of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors in modulating signalling pathways downstream of other types of receptor is well established, but the mechanisms underlying this modulation are not known. Recent data suggest that calcium-dependent signalling downstream of ITAM-coupled receptors regulates the amplitude and functional outcomes of cytokine and TLR signalling. In this Opinion article, I describe a model whereby the intensity of ITAM-dependent signalling and the balance of calcium signals relative to other ITAM-mediated signalling pathways determines whether cellular responses to cytokines and TLR ligands are increased or inhibited. This model describes mechanisms that explain how ITAM-coupled receptors regulate heterologous signalling pathways.
Ivashkiv
Lionel B
LB
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, 535 East 70th Street, New York, New York 10021, USA. IvashkivL@hss.edu
D020816:Amino Acid Motifs; D000818:Animals; D002118:Calcium / Q000276:immunology / Q000378:metabolism*; D020013:Calcium Signaling; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018448:Models, Immunological; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D051193:Toll-Like Receptors; D011494:Protein Kinases; D002118:Calcium
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