WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells
WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells
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DOI：
10.1084/jem.20030652
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发表时间：
2004-02-02
影响因子：
15.3
通讯作者：
Geha, RS
中科院分区：
文献类型：
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作者：
Kettner, A;Kumar, L;Geha, RS
Wiskott-Aldrich综合征蛋白质相互作用蛋白（Wiskott-Aldrich syndrome protein-interacting protein，WISK）稳定肌动蛋白丝，对免疫受体介导的信号转导非常重要，导致T和B细胞中肌动蛋白细胞骨架重排。在这里，我们报告的作用，在肥大细胞中的免疫球蛋白（IG）E（FcepsilonRI）的高亲和力受体下游的信号通路。WIP缺陷的骨髓源性肥大细胞（BMMC）在Fc ε RI连接后的去粘附和分泌白细胞介素6的能力受损。钙动员，磷酸化的Syk，磷脂酶C-g2，和c-Jun NH 2-末端激酶显着减少在WIP缺陷的BMMC。发现在FcepsilonRI连接后，Syk与Syk相关，并抑制Syk降解，如在WIP缺陷的BMMC中Syk水平显著降低所证明的。WIP缺陷的BMMC在其皮层下肌动蛋白网络中没有表现出明显的缺陷，并且当暴露于IgE包被的表面时，其形成突起的能力是正常的。然而，肌动蛋白的动力学变化和细胞形状的变化，遵循FcepsilonRI信号转导在WIP缺陷的BMMC改变。这些结果表明，FcepsilonRI介导的肥大细胞活化，调节Syk水平和肌动蛋白细胞骨架重排。
Wiskott-Aldrich syndrome protein-interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcepsilonRI) in mast cells. WIP-deficient bone marrow-derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcepsilonRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcepsilonRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.