Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools.
Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools.
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监督膜游泳：小型 G 蛋白救生员调节 PIPK 信号传导并监测细胞内 PtdIns(4,5)P2 库。
DOI：
10.1042/bj20060565
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Anderson,RichardA
中科院分区：
文献类型：
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作者：
Santarius,Megan;Lee,ChangHo;Anderson,RichardA
小G蛋白及其效应子对PIPK（phosphatidylinositol phosphate kinase，PIPK）和PtdIns（4，5）P2信号的调控是许多生物学功能的关键。通过选择性募集和激活不同的PIPK亚型，小G蛋白如Rho，Rac和Cdc 42调节肌动蛋白动力学和细胞因子依赖性细胞事件响应细胞外信号传导。这些活性影响许多过程，包括内吞作用、细菌渗透进入宿主细胞和溶细胞颗粒介导的靶向细胞杀伤。小G蛋白及其调节剂也通过移位和构象变化由磷酸肌醇调节。Arf家族小G蛋白在多个位点作为膜运输和肌动蛋白细胞骨架重塑的调节剂起作用，并调节包括磷脂酶D、磷脂酸、PIPKs和PtdIns（4，5）P2的反馈环，有助于增强PtdIns（4，5）P2介导的细胞事件和受体信号传导。Na+、Kir（内向整流K+）、Ca 2+和TRP（瞬时受体电位）离子通道由小G蛋白和PtdIns（4，5）P2的膜池调节。酵母磷脂酰肌醇4-磷酸5-激酶Mss 4和Its 3通过合成PtdIns（4，5）P2和下游信号转导途径Rom 2/Rho 2和Rgf 1/Rho参与抵抗鞘脂生物合成紊乱和维持细胞完整性。在这里，我们审查模型调节细胞内靶向的PIPKs的小G蛋白和其他调制器响应细胞外信号。我们还描述了PIPKs和小G蛋白的空间和时间交叉调节，这对许多细胞功能至关重要。
Regulation of PIPK (phosphatidylinositol phosphate kinase) and PtdIns(4,5)P2signalling by small G-proteins and their effectors is key to many biological functions. Through selective recruitment and activation of different PIPK isoforms, small G-proteins such as Rho, Rac and Cdc42 modulate actin dynamics and cytoskeleton-dependent cellular events in response to extracellular signalling. These activities affect a number of processes, including endocytosis, bacterial penetration into host cells and cytolytic granule-mediated targeted cell killing. Small G-proteins and their modulators are also regulated by phosphoinositides through translocation and conformational changes. Arf family small G-proteins act at multiple sites as regulators of membrane trafficking and actin cytoskeletal remodelling, and regulate a feedback loop comprising phospholipase D, phosphatidic acid, PIPKs and PtdIns(4,5)P2, contributing to enhancement of PtdIns(4,5)P2-mediated cellular events and receptor signalling. Na+, Kir (inwardly rectifying K+), Ca2+and TRP (transient receptor potential) ion channels are regulated by small G-proteins and membrane pools of PtdIns(4,5)P2. Yeast phosphatidylinositol 4-phosphate 5-kinases Mss4 and Its3 are involved in resistance against disturbance of sphingolipid biosynthesis and maintenance of cell integrity through the synthesis of PtdIns(4,5)P2and downstream signalling through the Rom2/Rho2 and Rgf1/Rho pathways. Here, we review models for regulated intracellular targeting of PIPKs by small G-proteins and other modulators in response to extracellular signalling. We also describe the spatial and temporal cross-regulation of PIPKs and small G-proteins that is critical for a number of cellular functions.