Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I {alpha}.
Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I {alpha}.
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DOI：
10.1084/jem.20041891
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发表时间：
2005-03-21
期刊：
影响因子：
--
通讯作者：
Kanaho Y
中科院分区：
文献类型：
--
作者：
Sasaki J;Sasaki T;Yamazaki M;Matsuoka K;Taya C;Shitara H;Takasuga S;Nishio M;Mizuno K;Wada T;Miyazaki H;Watanabe H;Iizuka R;Kubo S;Murata S;Chiba T;Maehama T;Hamada K;Kishimoto H;Frohman MA;Tanaka K;Penninger JM;Yonekawa H;Suzuki A;Kanaho Y
膜磷脂磷脂酰肌醇4,5 -二磷酸[PI(4,5)P2]是真核细胞中重要的信号换能器。然而，合成PI(4,5)P2的I型磷脂酰肌醇磷酸激酶（PIPKIs）的生理作用在很大程度上是未知的。在这里，我们发现PIPKI的α同工酶（PIPKIα）负调控肥大细胞功能和过敏反应。在体外，pipki α-缺陷肥大细胞在Fc受体- 1交联后，脱颗粒和细胞因子的产生增加。在体内，PIPKIα−/−小鼠表现出增强的被动皮肤和全身过敏反应。在PIPKIα - / -肥大细胞中，丝状肌动蛋白减少，在没有PIPKIα的情况下，在野生型肥大细胞中，用肌动蛋白聚合的药物抑制剂latrunculin处理后，也观察到脱颗粒增强。此外，在PIPKIα−/−肥大细胞中，Fc / RI与脂筏和Fc / RI介导的信号蛋白激活的关联增强。因此，PIPKIα是Fc i - RI介导的细胞反应和过敏反应的负调节因子，通过控制肌动蛋白细胞骨架和Fc i - RI信号传导的动力学起作用。我们的研究结果表明，不同的PIPKI亚型可能在功能上是专门化的。
The membrane phospholipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2] is a critical signal transducer in eukaryotic cells. However, the physiological roles of the type I phosphatidylinositol phosphate kinases (PIPKIs) that synthesize PI(4,5)P2 are largely unknown. Here, we show that the α isozyme of PIPKI (PIPKIα) negatively regulates mast cell functions and anaphylactic responses. In vitro, PIPKIα-deficient mast cells exhibited increased degranulation and cytokine production after Fcɛ receptor-I cross-linking. In vivo, PIPKIα−/− mice displayed enhanced passive cutaneous and systemic anaphylaxis. Filamentous actin was diminished in PIPKIα−/− mast cells, and enhanced degranulation observed in the absence of PIPKIα was also seen in wild-type mast cells treated with latrunculin, a pharmacological inhibitor of actin polymerization. Moreover, the association of FcɛRI with lipid rafts and FcɛRI-mediated activation of signaling proteins was augmented in PIPKIα−/− mast cells. Thus, PIPKIα is a negative regulator of FcɛRI-mediated cellular responses and anaphylaxis, which functions by controlling the actin cytoskeleton and dynamics of FcɛRI signaling. Our results indicate that the different PIPKI isoforms might be functionally specialized.
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影响因子：
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