PMID- 30282734
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20190416
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 115
IP  - 42
DP  - 2018 Oct 16
TI  - Raf kinase inhibitor protein negatively regulates FcepsilonRI-mediated mast cell 
      activation and allergic response.
PG  - E9859-E9868
LID - 10.1073/pnas.1805474115 [doi]
AB  - The signaling cascades triggered by the cross-linkage of immunoglobulin E (IgE) 
      with its high-affinity receptor (FcepsilonRI) on mast cells contribute to multiple 
      allergic disorders, such as asthma, rhinitis, and atopic dermatitis. Restraint of 
      intracellular signals for mast cell activation is essential to restore 
      homeostasis. In this study, we found that Raf kinase inhibitor protein (RKIP) 
      negatively regulated mast cell activation. RKIP-deficient mast cells showed 
      greater IgE-FcepsilonRI-mediated activation than wild-type mast cells. Consistently, 
      RKIP deficiency in mast cells rendered mice more sensitive to IgE-FcepsilonRI-mediated 
      allergic responses and ovalbumin-induced airway inflammation. Mechanistically, 
      RKIP interacts with the p85 subunit of PI3K, prevents it from binding to 
      GRB2-associated binding protein 2 (Gab2), and eventually inhibits the activation 
      of the PI3K/Akt/NF-kappaB complex and its downstream signaling. Furthermore, the 
      expression of RKIP was significantly down-regulated in the peripheral blood of 
      asthma patients and in the IgE-FcepsilonRI-stimulated mast cells. Collectively, our 
      findings not only suggest that RKIP plays an important role in controlling mast 
      cell-mediated allergic responses but also provide insight into therapeutic 
      targets for mast cell-related allergic diseases.
FAU - Lin, Wenlong
AU  - Lin W
AD  - Institute of Immunology, Zhejiang University School of Medicine, 310058 Hangzhou, 
      People's Republic of China.
FAU - Su, Fasheng
AU  - Su F
AD  - Institute of Immunology, Zhejiang University School of Medicine, 310058 Hangzhou, 
      People's Republic of China.
FAU - Gautam, Rahul
AU  - Gautam R
AD  - Institute of Immunology, Zhejiang University School of Medicine, 310058 Hangzhou, 
      People's Republic of China.
FAU - Wang, Ning
AU  - Wang N
AD  - Institute of Immunology, Zhejiang University School of Medicine, 310058 Hangzhou, 
      People's Republic of China.
FAU - Zhang, Yuanyuan
AU  - Zhang Y
AD  - Department of Respiratory Medicine, Children's Hospital, Zhejiang University 
      School of Medicine, 310058 Hangzhou, People's Republic of China.
FAU - Wang, Xiaojian
AU  - Wang X
AUID- ORCID: 0000-0001-8232-0558
AD  - Institute of Immunology, Zhejiang University School of Medicine, 310058 Hangzhou, 
      People's Republic of China; wangxiaojian@cad.zju.edu.cn.
AD  - Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, 310003 Hangzhou, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181003
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (PEBP1 protein, human)
RN  - 0 (Phosphatidylethanolamine Binding Protein)
RN  - 0 (Raf kinase inhibitory protein, mouse)
RN  - 0 (Receptors, IgE)
SB  - IM
MH  - Anaphylaxis/*immunology/metabolism
MH  - Animals
MH  - Asthma/*immunology/metabolism
MH  - Cell Degranulation
MH  - Cells, Cultured
MH  - Child
MH  - Humans
MH  - Mast Cells/*immunology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Phosphatidylethanolamine Binding Protein/*physiology
MH  - Receptors, IgE/*metabolism
MH  - Signal Transduction
PMC - PMC6196501
OTO - NOTNLM
OT  - FcepsilonRI signaling
OT  - RKIP
OT  - allergic response
OT  - asthma
OT  - mast cell
COIS- The authors declare no conflict of interest.
EDAT- 2018/10/05 06:00
MHDA- 2018/12/18 06:00
PMCR- 2019/04/03
CRDT- 2018/10/05 06:00
PHST- 2018/10/05 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/10/05 06:00 [entrez]
PHST- 2019/04/03 00:00 [pmc-release]
AID - 1805474115 [pii]
AID - 201805474 [pii]
AID - 10.1073/pnas.1805474115 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9859-E9868. doi: 
      10.1073/pnas.1805474115. Epub 2018 Oct 3.