的磷脂酰肌醇3 -磷酸磷酸酶myotubularin相关蛋白6 (MTMR6)是-调节器的Ca2 +激活KCa3.1 K +通道。
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斯利瓦斯塔瓦年代,李Z,林L,刘G, Ko K, Coetzee佤邦,最好是
的磷脂酰肌醇3 -磷酸磷酸酶myotubularin相关蛋白6 (MTMR6)是-调节器的Ca2 +激活KCa3.1 K +通道。
摩尔细胞杂志。2005;25 (9):3630 - 8。
- PubMed ID
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15831468 (在PubMed]
- 文摘
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Myotubularins (mtm)属于一个大亚磷酸酯酶的脱去磷酸的3 '位置-磷酸磷脂酰肌醇(PI (3) P)和π(3、5)P (2)。MTM1突变在x连锁myotubular肌病,MTMR2综合症腓骨肌萎缩和MTMR13突变。然而,对一般的机制(s), mtm监管或特定的生物过程由不同的mtm。我们发现了一个钙激活钾通道(2 +),K (Ca) 3.1(也称为KCa4, IKCa1、hIK1或SK4),专门与MTMR6交互亚科的mtm通过卷曲螺旋(CC)域蛋白质。超表达MTMR6抑制K (Ca) 3.1通道活动,这需要抑制MTMR6 CC和磷酸酶域。这种抑制是特定的;MTM1, MTM密切相关,不抑制3.1 K (Ca)。然而,的嵌合MTM1 MTM1 CC域是MTMR6 CC交换域抑制K (Ca) 3.1,表明MTM CC域足以赋予目标特异性。3.1 K (Ca)也抑制了π(3)激酶抑制剂LY294002渥曼青霉素,这种抑制获救的π(3)P,但不是其他磷酸肌醇,补丁吸管的解决方案。π(3)P也救出了3.1 K (Ca)的抑制MTMR6超表达。 These data, when taken together, indicate that K(Ca)3.1 is regulated by PI(3)P and that MTMR6 inhibits K(Ca)3.1 by dephosphorylating the 3' position of PI(3)P, possibly leading to decreased PI(3)P in lipid microdomains adjacent to K(Ca)3.1. K(Ca)3.1 plays important roles in controlling proliferation by T cells, vascular smooth muscle cells, and some cancer cell lines. Thus, our findings not only provide unique insights into the regulation of K(Ca)3.1 channel activity but also raise the possibility that MTMs play important roles in the negative regulation of T cells and in conditions associated with pathological cell proliferation, such as cancer and atherosclerosis.