期刊
CURRENT ALLERGY AND ASTHMA REPORTS
卷 8, 期 1, 页码 14-20出版社
CURRENT MEDICINE GROUP
DOI: 10.1007/s11882-008-0004-z
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资金
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZIAAR041155, Z01AR041155, Z01AR041101, ZIAAR041101] Funding Source: NIH RePORTER
- Intramural NIH HHS Funding Source: Medline
Mast cell activation via the high-affinity immunoglobulin (Ig) E receptor Fc epsilon RI is a topic of extensive investigation with therapeutic potential in allergic disease. The protein tyrosine kinases Fyn, Lyn, and Syk are intimately linked with the early events initiated by allergen-mediated aggregation of IgE-occupied Fc epsilon RI. Fyn and Lyn initiate signaling events that are organized by adaptor molecules, which compartmentalize and coordinate the activity of activated protein and lipid kinases and phospholipases to generate lipid products essential for signal amplification and mast cell function. Fyn and Lyn counter-regulate phosphaticlylinositol 3-OH kinase (PI3K), controlling the produced amount of phosphaticlylinositol (3,4,5)-trisphosphate (PIP3), a key regulator of mast cell degranulation. Fyn and Lyn also activate sphingosine kinases (SphK), which generate sphingosine-1-phosphate (S1P), thus contributing to mast cell chemotaxis and degranulation. Here, we summarize the current knowledge and future challenges and directions.
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