Inhibition of immune responses by ITAM-bearing receptors.
Cells of the immune system possess many multisubunit receptors that are composed of a ligand-binding subunit associated with distinct signaling adaptors containing one or more immunoreceptor tyrosine-based activation motifs (ITAMs). These receptors include the T cell receptor, the B cell receptor, and many Fc receptors, as well as families of activating receptors on myeloid and natural killer cells. Receptors that associate with ITAM-containing adaptors classically have been viewed as transducing activating signals involving phosphorylation of the tyrosines within the ITAM and recruitment of Syk family tyrosine kinases. Receptors associated with ITAM-containing adaptors in myeloid cells have also been implicated in inhibition of cellular activation. Here, we discuss these new negative roles for signaling by receptors that associate with ITAM-bearing adaptors in myeloid and other cell types within the immune system.
Hamerman
Jessica A
JA
Department of Microbiology and Immunology, Cancer Research Institute, University of California, Box 0414, HSE1001, San Francisco, CA 94143-0414, USA.
Lanier
Lewis L
LL
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020816:Amino Acid Motifs; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D020013:Calcium Signaling; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004792:Enzyme Precursors / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000276:immunology*; D008262:Macrophage Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D022423:Myeloid Cells / Q000276:immunology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D011961:Receptors, Fc / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000502:physiology*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D016207:Cytokines; D004792:Enzyme Precursors; C036832:Fc(alpha) receptor; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C484963:Tyrobp protein, mouse; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; D017027:Protein Tyrosine Phosphatases