PMID- 15180535
OWN - NLM
STAT- MEDLINE
DCOM- 20040629
LR  - 20190728
IS  - 1381-6128 (Print)
IS  - 1381-6128 (Linking)
VI  - 10
IP  - 15
DP  - 2004
TI  - Modulation of the Fcepsilon receptor I signaling by tyrosine kinase inhibitors: 
      search for therapeutic targets of inflammatory and allergy diseases.
PG  - 1727-37
AB  - Mast cells and basophils are major effector cells in the immunoglobulin E 
      (IgE)-dependent allergic reactions as well as in the innate immunity. They are 
      distributed throughout the body and, upon allergen exposure, are stimulated via 
      the high affinity IgE receptor (FcepsilonRI) to release several pro-inflammatory 
      mediators such as leukotrienes, immunoregulatory cytokines and histamine. 
      FcepsilonRI-mediated signaling is initiated by tyrosine phosphorylation of 
      FcepsilonRI subunits by Src family kinase Lyn, which is followed by an activation 
      of Syk/Zap family kinase Syk. The activated kinases then in turn phosphorylate 
      and activate other enzymes [phospholipase Cgamma (PLCgamma) isoforms, 
      phosphatidylinositol-3 kinase (PI3K) isoforms, protein kinase C (PKC) isoforms, 
      Bruton's tyrosine kinase (Btk) and others], adaptors [linker for activation of T 
      cells (LAT), Cbl, Grb2 and others] and GTP exchange factors/GTPases (Vav, Ras, 
      Rho, and others), and subsequently induce the mobilization of stored and 
      extracellular Ca(2+). These and other biochemical events lead within seconds and 
      minutes to the secretory response and later to the production of chemokines. This 
      review is focused on the use of tyrosine kinase inhibitors specific for Src 
      family kinases (PP1/PP2, SU6656 and CT5269), Syk kinase (piceatannol, ER-27319 
      and BAY 61-3606) and Btk (terreic acid and LFM-A13) for a modulation of 
      FcepsilonRI-mediated signaling in mast cells. Potential use of the inhibitors in 
      the treatment of inflammatory and allergy diseases as well as future directions 
      in the development of highly specific tyrosine kinases inhibitors of new 
      generations and their use in an intended modulation of mast cell signaling are 
      discussed.
FAU - Luskova, Petra
AU  - Luskova P
AD  - Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 
      Prague, Czech Republic.
FAU - Draber, Petr
AU  - Draber P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptors, IgE)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Enzyme Inhibitors/metabolism/*therapeutic use
MH  - Humans
MH  - Hypersensitivity/*drug therapy/immunology
MH  - Inflammation/*drug therapy/immunology
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism
MH  - Receptors, IgE/*metabolism/physiology
MH  - Signal Transduction/*drug effects/immunology
RF  - 78
EDAT- 2004/06/08 05:00
MHDA- 2004/06/30 05:00
CRDT- 2004/06/08 05:00
PHST- 2004/06/08 05:00 [pubmed]
PHST- 2004/06/30 05:00 [medline]
PHST- 2004/06/08 05:00 [entrez]
AID - 10.2174/1381612043384538 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2004;10(15):1727-37. doi: 10.2174/1381612043384538.