Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
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Enzyme
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Query: UNIPROT:P15088 (
mast cell
)
14,925
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Aggregation of the high-affinity IgE receptor (FcepsilonRI) on mast cells initiates signaling pathways leading to degranulation and cytokine release. It has been reported that SHIP-1 negatively regulates FcepsilonRI-triggered pathways but it is unknown whether its homologous protein
SHIP-2
has the same function. We have used a lentiviral-based RNA interference technique to obtain
SHIP-2
knockdown bone marrow-derived mast cells (BMMCs) and have found that elimination of
SHIP-2
results in both increased
mast cell
degranulation and cytokine (IL-4 and IL-13) gene expression upon FcepsilonRI stimulation. Elimination of
SHIP-2
from BMMCs has no effect on FcepsilonRI-triggered calcium flux, tyrosine phosphorylation of MAPKs or in actin depolymerization following activation. Rather, we observe that absence of
SHIP-2
results in increased activation of the small GTPase Rac-1 and in enhanced microtubule polymerization upon FcepsilonRI engagement. Coimmunoprecipitation experiments in rat basophilic leukemia (RBL 2H3) cells show that
SHIP-2
interacts with the FcepsilonRI beta-chain, Gab2 and Lyn and that unlike SHIP-1, it does not associate with SHC in mast cells. Our results report a negative regulatory role of
SHIP-2
on
mast cell
activation that is calcium independent and distinct from the regulation by SHIP-1.
...
PMID:The inositol 5'-phosphatase SHIP-2 negatively regulates IgE-induced mast cell degranulation and cytokine production. 1757 26
