Publication Date:
2014-02-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188507/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188507/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Ryo -- Leach, Sarah -- Liu, Wenhua -- Ralston, Evelyn -- Scheffel, Jorg -- Zhang, Weiguo -- Lowell, Clifford A -- Rivera, Juan -- R01 AI065495/AI/NIAID NIH HHS/ -- R01 AI068150/AI/NIAID NIH HHS/ -- ZIA AR041101-20/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 28;343(6174):1021-5. doi: 10.1126/science.1246976. Epub 2014 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24505132" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/metabolism
;
Amino Acid Transport System y+/metabolism
;
Animals
;
Antigens, CD98 Light Chains/metabolism
;
Cattle
;
Cell Movement
;
Chemokines/metabolism
;
Dinitrophenols
;
Immunoglobulin E/*metabolism
;
Inflammation/immunology
;
Mast Cells/*immunology
;
Membrane Proteins/metabolism
;
Mice
;
Phosphoproteins/metabolism
;
Proto-Oncogene Proteins/metabolism
;
Receptors, IgE/*metabolism
;
src-Family Kinases/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
