PMID- 24023254
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20211203
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 6
IP  - 292
DP  - 2013 Sep 10
TI  - The scaffold protein prohibitin is required for antigen-stimulated signaling in 
      mast cells.
PG  - ra80
LID - 10.1126/scisignal.2004098 [doi]
AB  - The protein prohibitin (PHB) is implicated in diverse cellular processes, 
      including cell signaling, transcriptional control, and mitochondrial function. We 
      found that PHB was abundant in the intracellular granules of mast cells, which 
      are critical for allergic responses to antigens. Thus, we investigated whether 
      PHB played a role in signaling mediated by the high-affinity receptor for 
      antigen-bound immunoglobulin E (IgE), FcepsilonRI. PHB-specific small interfering RNAs 
      (siRNAs) inhibited antigen-mediated signaling, degranulation, and cytokine 
      secretion by mast cells in vitro. Knockdown of PHB inhibited the 
      antigen-dependent association of the tyrosine kinase Syk with FcepsilonRI and inhibited 
      the activation of Syk. Fractionation studies revealed that PHB translocated from 
      intracellular granules to plasma membrane lipid rafts in response to antigen, and 
      knockdown of PHB suppressed the movement of FcepsilonRIgamma and Syk into lipid rafts. 
      Tyrosine phosphorylation of PHB by Lyn was observed early after exposure to 
      antigen, and point mutations in PHB indicated that Tyr(114) and Tyr(259) were 
      required for the recruitment of Syk to FcepsilonRIgamma and mast cell activation. In mice, 
      PHB-specific siRNAs inhibited antigen-initiated mast cell degranulation, passive 
      cutaneous anaphylaxis, and passive systemic anaphylaxis. Together, these results 
      suggest that PHB is essential for FcepsilonRI-mediated mast cell activation and 
      allergic responses in vivo, raising the possibility that PHB might serve as a 
      therapeutic target for the treatment of allergic diseases.
FAU - Kim, Do Kyun
AU  - Kim DK
AD  - 1Department of Immunology and Physiology and Functional Genomics Institute, 
      College of Medicine, Konkuk University, Chungju 380-701, Korea.
FAU - Kim, Hyuk Soon
AU  - Kim HS
FAU - Kim, A-Ram
AU  - Kim AR
FAU - Jang, Geun Hyo
AU  - Jang GH
FAU - Kim, Hyun Woo
AU  - Kim HW
FAU - Park, Young Hwan
AU  - Park YH
FAU - Kim, Bokyung
AU  - Kim B
FAU - Park, Yeong Min
AU  - Park YM
FAU - Beaven, Michael A
AU  - Beaven MA
FAU - Kim, Young Mi
AU  - Kim YM
FAU - Choi, Wahn Soo
AU  - Choi WS
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130910
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Antigens)
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Prohibitins)
RN  - 0 (Receptors, IgE)
RN  - 0 (Repressor Proteins)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens/*immunology
MH  - Blotting, Western
MH  - Cell Degranulation/immunology
MH  - Cells, Cultured
MH  - Cytokines/immunology/metabolism
MH  - Immunoglobulin E/immunology/metabolism
MH  - Intracellular Signaling Peptides and Proteins/immunology/metabolism
MH  - Male
MH  - Mast Cells/*immunology/metabolism/physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microscopy, Confocal
MH  - Models, Immunological
MH  - Mutation
MH  - Passive Cutaneous Anaphylaxis/genetics/immunology
MH  - Phosphorylation/immunology
MH  - Prohibitins
MH  - Protein Binding/immunology
MH  - Protein-Tyrosine Kinases/immunology/metabolism
MH  - RNA Interference
MH  - Receptors, IgE/immunology/metabolism
MH  - Repressor Proteins/genetics/*immunology/metabolism
MH  - Signal Transduction/genetics/*immunology
MH  - Syk Kinase
MH  - Tyrosine/immunology/metabolism
EDAT- 2013/09/12 06:00
MHDA- 2014/04/15 06:00
CRDT- 2013/09/12 06:00
PHST- 2013/09/12 06:00 [entrez]
PHST- 2013/09/12 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - 6/292/ra80 [pii]
AID - 10.1126/scisignal.2004098 [doi]
PST - epublish
SO  - Sci Signal. 2013 Sep 10;6(292):ra80. doi: 10.1126/scisignal.2004098.