PMID- 24505132
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20240508
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 343
IP  - 6174
DP  - 2014 Feb 28
TI  - Molecular editing of cellular responses by the high-affinity receptor for IgE.
PG  - 1021-5
LID - 10.1126/science.1246976 [doi]
AB  - 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.
FAU - Suzuki, Ryo
AU  - Suzuki R
AD  - Laboratory of Molecular Immunogenetics, National Institute of Arthritis and 
      Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
FAU - Leach, Sarah
AU  - Leach S
FAU - Liu, Wenhua
AU  - Liu W
FAU - Ralston, Evelyn
AU  - Ralston E
FAU - Scheffel, Jorg
AU  - Scheffel J
FAU - Zhang, Weiguo
AU  - Zhang W
FAU - Lowell, Clifford A
AU  - Lowell CA
FAU - Rivera, Juan
AU  - Rivera J
LA  - eng
GR  - R01 AI065495/AI/NIAID NIH HHS/United States
GR  - R01 AI068150/AI/NIAID NIH HHS/United States
GR  - ZIA AR041101-20/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20140206
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amino Acid Transport System y+)
RN  - 0 (Chemokines)
RN  - 0 (Dinitrophenols)
RN  - 0 (Fusion Regulatory Protein 1, Light Chains)
RN  - 0 (Lat protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, IgE)
RN  - 0 (SLC7A8 protein, mouse)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.2 (proto-oncogene proteins c-fgr)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
CIN - Science. 2014 Feb 28;343(6174):982-3. PMID: 24578573
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Amino Acid Transport System y+/metabolism
MH  - Animals
MH  - Cattle
MH  - Cell Movement
MH  - Chemokines/metabolism
MH  - Dinitrophenols
MH  - Fusion Regulatory Protein 1, Light Chains/metabolism
MH  - Immunoglobulin E/*metabolism
MH  - Inflammation/immunology
MH  - Mast Cells/*immunology
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Phosphoproteins/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Receptors, IgE/*metabolism
MH  - src-Family Kinases/metabolism
PMC - PMC4188507
MID - NIHMS631978
COIS- The authors declare no conflicts of interest.
EDAT- 2014/02/08 06:00
MHDA- 2014/04/10 06:00
PMCR- 2015/02/28
CRDT- 2014/02/08 06:00
PHST- 2014/02/08 06:00 [entrez]
PHST- 2014/02/08 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
PHST- 2015/02/28 00:00 [pmc-release]
AID - science.1246976 [pii]
AID - 10.1126/science.1246976 [doi]
PST - ppublish
SO  - Science. 2014 Feb 28;343(6174):1021-5. doi: 10.1126/science.1246976. Epub 2014 
      Feb 6.