PMID- 16785509
OWN - NLM
STAT- MEDLINE
DCOM- 20060809
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 177
IP  - 1
DP  - 2006 Jul 1
TI  - Flotillin-1 regulates IgE receptor-mediated signaling in rat basophilic leukemia 
      (RBL-2H3) cells.
PG  - 147-54
AB  - Cross-linking of high-affinity IgE receptors by multivalent Ag on mast cells (rat 
      basophilic leukemia (RBL)-2H3) induces the phosphorylation of ITAM motifs of an 
      IgE receptor by Src family tyrosine kinase, Lyn. The phosphorylation of IgE 
      receptors is followed by a series of intracellular signals, such as Ca(2+) 
      mobilization, MAPK activation, and degranulation. Therefore, Lyn is a key 
      molecule in the activation of mast cells, but the molecular mechanisms for the 
      activation of Lyn are still unclear. Recently, it is suggested that the 
      localization of Lyn in lipid rafts is critical for its activation in several cell 
      lines, although the precise mechanism is still unknown. In this study, we found 
      that flotillin-1, which is localized in lipid rafts, is involved in the process 
      of Lyn activation. We obtained flotillin-1 knockdown (KD)(2) rat basophilic 
      leukemia (RBL)-2H3 cells, which express a low level of flotillin-1. In the 
      flotillin-1 KD cells, we observed a significant decrease in Ca(2+) mobilization, 
      the phosphorylation of ERKs, tyrosine phosphorylation of the gamma-subunit of IgE 
      receptor, and IgE receptor-mediated degranulation. We also found that flotillin-1 
      is constitutively associated with Lyn in lipid rafts in RBL-2H3 cells, and Ag 
      stimulation induced the augmentation of flotillin-1 binding to Lyn, resulting in 
      enhancement of kinase activity of Lyn. These results suggest that flotillin-1 is 
      an essential molecule in IgE receptor-mediated mast cell activation, and 
      regulates the kinase activity of Lyn in lipid rafts.
FAU - Kato, Naoto
AU  - Kato N
AD  - Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, 
      Mizuho-ku, Nagoya 467-8603, Japan.
FAU - Nakanishi, Mamoru
AU  - Nakanishi M
FAU - Hirashima, Naohide
AU  - Hirashima N
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, IgE)
RN  - 0 (flotillins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.2 (lyn protein-tyrosine kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Signaling/physiology
MH  - Cell Degranulation/physiology
MH  - Cell Line, Tumor
MH  - Enzyme Activation/physiology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Leukemia, Basophilic, Acute/enzymology/immunology/metabolism
MH  - Mast Cells/enzymology/*immunology/*metabolism
MH  - Membrane Microdomains/enzymology/immunology/metabolism
MH  - Membrane Proteins/deficiency/genetics/*physiology
MH  - Phosphorylation
MH  - Rats
MH  - Receptors, IgE/biosynthesis/metabolism/*physiology
MH  - *Signal Transduction/immunology
MH  - Transfection
MH  - Tyrosine/metabolism
MH  - src-Family Kinases/metabolism
EDAT- 2006/06/21 09:00
MHDA- 2006/08/10 09:00
CRDT- 2006/06/21 09:00
PHST- 2006/06/21 09:00 [pubmed]
PHST- 2006/08/10 09:00 [medline]
PHST- 2006/06/21 09:00 [entrez]
AID - 177/1/147 [pii]
AID - 10.4049/jimmunol.177.1.147 [doi]
PST - ppublish
SO  - J Immunol. 2006 Jul 1;177(1):147-54. doi: 10.4049/jimmunol.177.1.147.