| Autor: |
Miah SM; Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Hatani T, Qu X, Yamamura H, Sada K |
| Jazyk: |
angličtina |
| Zdroj: |
Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2004 Nov; Vol. 9 (11), pp. 993-1004. |
| DOI: |
10.1111/j.1365-2443.2004.00784.x |
| Abstrakt: |
Adaptor protein 3BP2 positively regulates the high affinity IgE receptor (FcepsilonRI)-mediated activation of degranulation in mast cells. Genetic study identified the point mutations of 3BP2 gene in human-inherited disease cherubism. The multiple cysts in cherubism lesion of jaw bones are filled with the activated osteoclasts and stromal cells, including mast cells. By over-expression study using rat basophilic leukaemia RBL-2H3 mast cells, we have analysed the effect of the point mutations on the function of 3BP2 protein, which plays a positive regulatory role on FcepsilonRI-mediated mast cell activation. Over-expression of 3BP2 mutants suppressed the antigen-induced degranulation and cytokine gene transcription. Antigen-induced phosphorylation of Vav1, activation of Rac1, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen activated protein kinase (MAPK), inhibitor of nuclear factor kappaB kinase (IKK) and nuclear factor of activated T cells (NFAT) were all impaired in the cells over-expressing the cherubism mutants of 3BP2. Furthermore, cherubism mutations of 3BP2 may abrogate the binding ability to interact with chaperone protein 14-3-3. These results demonstrate that over-expression of the mutant form of 3BP2 inhibits the antigen-induced mast cell activation. It suggests that point mutations of 3BP2 gene cause the dysfunction of 3BP2 in vivo. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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