The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells.
The adapter proteins DAP12 and FcRgamma associate with a wide spectrum of receptors in a variety of innate immune cells to mediate intracellular signaling pathways when their cognate receptor is engaged. These adapter proteins are coupled to their receptors through charged residues within the transmembrane regions of the adapter and receptor. DAP12 and FcRgamma contain specific protein domains (referred to as immunoreceptor tyrosine-based activation motifs) that serve as the substrates and docking sites for kinases, allowing amplification of intracellular signaling reactions. Recent research has broadened the repertoire of receptors that utilize these adapters for signaling to include not only novel immunoglobulin superfamily members but also cytokine receptors, integrins, and other adhesion molecules. There is abundant evidence that these multifunctional signaling adapters also mediate inhibitory activity, downmodulating signaling from Toll-like receptors and other heterologous receptors. In this review, we discuss the newly described receptors that utilize DAP12 and/or FcRgamma adapters to modulate innate immune responses.
Hamerman
Jessica A
JA
Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Ni
Minjian
M
Killebrew
Justin R
JR
Chu
Ching-Liang
CL
Lowell
Clifford A
CA
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017452:Receptors, IgG; C110546:TYROBP protein, human; D014443:Tyrosine