PMID- 14604964
OWN - NLM
STAT- MEDLINE
DCOM- 20040420
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 5
DP  - 2004 Mar 1
TI  - Negative regulation of FcepsilonRI-mediated mast cell activation by a 
      ubiquitin-protein ligase Cbl-b.
PG  - 1779-86
AB  - Aggregation of the high-affinity immunoglobulin E (IgE) receptor (FcepsilonRI) on 
      mast cells induces a number of biochemical events, including protein-tyrosine 
      phosphorylation leading to degranulation and multiple cytokine gene 
      transcription. Here, we have demonstrated that a second member of the Cbl family 
      of ubiquitin-protein ligase Cbl-b translocates into the lipid raft after 
      FcepsilonRI engagement. Overexpression of Cbl-b in the lipid raft inhibits 
      FcepsilonRI-mediated degranulation and cytokine gene transcription through the 
      distinct mechanism. A point mutation of Cys373 in the RING finger domain of Cbl-b 
      abrogates the suppression of FcepsilonRI-mediated degranulation but not cytokine 
      gene transcription. The antigen-induced tyrosine phosphorylation of FcepsilonRI, 
      Syk, phospholipase C-gamma (PLC-gamma), activation of c-Jun N-terminal kinase 
      (JNK), extracellular signal regulated kinase (ERK), inhibitor of nuclear factor 
      kappaB kinase (IKK), and Ca++ influx were all suppressed in the cells 
      overexpressing Cbl-b in the lipid raft. In particular, the expression amount of 
      Gab2 protein and thereby its FcepsilonRI-mediated tyrosine phosphorylation were 
      dramatically down-regulated by ubiquitin-protein ligase activity of Cbl-b. These 
      results suggest that Cbl-b is a negative regulator of both Lyn-Syk-LAT and 
      Gab2mediated complementary signaling pathways in FcepsilonRI-mediated mast cell 
      activation.
FAU - Qu, Xiujuan
AU  - Qu X
AD  - Division of Proteomics, Department of Genome Sciences, Kobe University Graduate 
      School of Medicine, Kobe, Japan.
FAU - Sada, Kiyonao
AU  - Sada K
FAU - Kyo, Shinkou
AU  - Kyo S
FAU - Maeno, Koichiro
AU  - Maeno K
FAU - Miah, S M Shahjahan
AU  - Miah SM
FAU - Yamamura, Hirohei
AU  - Yamamura H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031106
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cblb protein, rat)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, IgE)
RN  - 0 (Ubiquitin)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.3.2.27 (CBLB protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Calcium/metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Enzyme Precursors/metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - I-kappa B Kinase
MH  - Intracellular Signaling Peptides and Proteins
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - Lipid Metabolism
MH  - MAP Kinase Kinase 4
MH  - Mast Cells/*cytology
MH  - Membrane Microdomains/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation
MH  - Phospholipase C gamma
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-cbl
MH  - Rats
MH  - Receptors, IgE/*biosynthesis/genetics
MH  - Ribonucleases/metabolism
MH  - Signal Transduction
MH  - Subcellular Fractions
MH  - Syk Kinase
MH  - Time Factors
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Type C Phospholipases/metabolism
MH  - Tyrosine/metabolism
MH  - Ubiquitin/metabolism
MH  - *Ubiquitin-Protein Ligases
MH  - beta-N-Acetylhexosaminidases/metabolism
EDAT- 2003/11/08 05:00
MHDA- 2004/04/21 05:00
CRDT- 2003/11/08 05:00
PHST- 2003/11/08 05:00 [pubmed]
PHST- 2004/04/21 05:00 [medline]
PHST- 2003/11/08 05:00 [entrez]
AID - S0006-4971(20)50091-8 [pii]
AID - 10.1182/blood-2003-07-2260 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 1;103(5):1779-86. doi: 10.1182/blood-2003-07-2260. Epub 2003 Nov 
      6.