title: Molecular editing of cellular responses by the high-affinity receptor for IgE.
abstract: Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar receptor phosphorylation; however, differences were observed in receptor cluster size, mobility, distribution, and the cells' effector responses. Low-affinity stimulation increased receptor association with the Src family kinase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2. LAT1-dependent calcium signals required for mast cell degranulation were dampened, but the role of LAT2 in chemokine production was enhanced, altering immune cell recruitment at the site of inflammation. These findings uncover how receptor discrimination of stimulus strength can be interpreted as distinct in vivo outcomes.
authors: Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
authors: Ryo
authors: R
authors: Suzuki
authors: Sarah
authors: S
authors: Leach
authors: Wenhua
authors: W
authors: Liu
authors: Evelyn
authors: E
authors: Ralston
authors: Jörg
authors: J
authors: Scheffel
authors: Weiguo
authors: W
authors: Zhang
authors: Clifford A
authors: CA
authors: Lowell
authors: Juan
authors: J
authors: Rivera
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D027182:Amino Acid Transport System y+ / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D004140:Dinitrophenols; D027301:Fusion Regulatory Protein 1, Light Chains / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D027182:Amino Acid Transport System y+; D018925:Chemokines; D004140:Dinitrophenols; D027301:Fusion Regulatory Protein 1, Light Chains; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; C518286:SLC7A8 protein, mouse; D007073:Immunoglobulin E; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases