Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling.
Receptors for immunoglobulin Fc regions play multiple critical roles in the immune system, mediating functions as diverse as phagocytosis, triggering degranulation of basophils and mast cells, promoting immunoglobulin class switching, and preventing excessive activation. Transmembrane signaling associated with these functions is mediated primarily by two amino acid sequence motifs, ITAMs (immunoreceptor tyrosine-based activation motifs) and ITIMs (immunoreceptor tyrosine-based inhibition motifs) that act as the receptors' interface with activating and inhibitory signaling pathways, respectively. While ITAMs mobilize activating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol-lipid phosphatases. In this review, we will discuss our current understanding of signaling by these receptors/motifs and their sometimes blurred lines of function.
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
Andrew
A
Getahun
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
John C
JC
Cambier
D020816:Amino Acid Motifs; D000818:Animals; D000893:Anti-Inflammatory Agents; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology / Q000627:therapeutic use; D056747:Immunomodulation; D008024:Ligands; D011485:Protein Binding / Q000276:immunology; D054730:Protein Interaction Domains and Motifs; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011961:Receptors, Fc / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D008024:Ligands; D011961:Receptors, Fc; D017452:Receptors, IgG; D017027:Protein Tyrosine Phosphatases
Fc receptors; ITAMs; ITIMs; SHIP; SHP; signal transduction