PMID- 27786273
OWN - NLM
STAT- MEDLINE
DCOM- 20180827
LR  - 20191210
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 7
DP  - 2016 Oct 27
TI  - The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell 
      activation.
PG  - 13198
LID - 10.1038/ncomms13198 [doi]
LID - 13198
AB  - Cross-linkage of the high-affinity immunoglobulin E (IgE) receptor (FcvarepsilonRI) on 
      mast cells by antigen ligation has a critical role in the pathology of 
      IgE-dependent allergic disorders, such as anaphylaxis and asthma. Restraint of 
      intracellular signal transduction pathways that promote release of mast 
      cell-derived pro-inflammatory mediators is necessary to dampen activation and 
      restore homoeostasis. Here we show that the ligase Nedd4-2 and the adaptor Ndfip1 
      (Nedd4 family interacting protein 1) limit the intensity and duration of 
      IgE-FcvarepsilonRI-induced positive signal transduction by ubiquitinating phosphorylated 
      Syk, a tyrosine kinase that is indispensable for downstream FcvarepsilonRI signalosome 
      activity. Importantly, loss of Nedd4-2 or Ndfip1 in mast cells results in 
      exacerbated and prolonged IgE-mediated cutaneous anaphylaxis in vivo. Our 
      findings reveal an important negative regulatory function for Nedd4-2 and Ndfip1 
      in IgE-dependent mast cell activity.
FAU - Yip, Kwok Ho
AU  - Yip KH
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
FAU - Kolesnikoff, Natasha
AU  - Kolesnikoff N
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
FAU - Hauschild, Nicholas
AU  - Hauschild N
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
FAU - Biggs, Lisa
AU  - Biggs L
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
FAU - Lopez, Angel F
AU  - Lopez AF
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
AD  - School of Medicine, University of Adelaide, Adelaide, South Australia 5005, 
      Australia.
FAU - Galli, Stephen J
AU  - Galli SJ
AD  - Departments of Pathology and of Microbiology and Immunology, and the Sean N. 
      Parker Center for Allergy and Asthma Research, Stanford University School of 
      Medicine, Stanford, California 94305-5176, USA.
FAU - Kumar, Sharad
AU  - Kumar S
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
AD  - School of Medicine, University of Adelaide, Adelaide, South Australia 5005, 
      Australia.
FAU - Grimbaldeston, Michele A
AU  - Grimbaldeston MA
AD  - Centre for Cancer Biology, University of South Australia and SA Pathology, 
      Adelaide, South Australia 5000, Australia.
AD  - School of Medicine, University of Adelaide, Adelaide, South Australia 5005, 
      Australia.
AD  - OMNI-Biomarker Development, Genentech Inc., South San Francisco, California 
      94080, USA.
LA  - eng
GR  - R01 AR067145/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161027
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Ndfip1 protein, mouse)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases)
RN  - EC 2.3.2.26 (Nedd4l protein, mouse)
RN  - EC 2.7.10.2 (Syk Kinase)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Carrier Proteins/genetics/*immunology/metabolism
MH  - Cells, Cultured
MH  - Cytokines/immunology/metabolism
MH  - Female
MH  - Immunoglobulin E/*immunology/metabolism
MH  - Intercellular Signaling Peptides and Proteins
MH  - Male
MH  - Mast Cells/*immunology/metabolism/transplantation
MH  - Membrane Proteins/genetics/*immunology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Nedd4 Ubiquitin Protein Ligases/genetics/*immunology/metabolism
MH  - Passive Cutaneous Anaphylaxis/genetics/immunology
MH  - Receptors, IgE/immunology/metabolism
MH  - Syk Kinase/immunology/metabolism
PMC - PMC5095291
EDAT- 2016/10/28 06:00
MHDA- 2018/08/28 06:00
PMCR- 2016/10/27
CRDT- 2016/10/28 06:00
PHST- 2015/12/18 00:00 [received]
PHST- 2016/09/11 00:00 [accepted]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2018/08/28 06:00 [medline]
PHST- 2016/10/28 06:00 [entrez]
PHST- 2016/10/27 00:00 [pmc-release]
AID - ncomms13198 [pii]
AID - 10.1038/ncomms13198 [doi]
PST - epublish
SO  - Nat Commun. 2016 Oct 27;7:13198. doi: 10.1038/ncomms13198.