The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity
The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity
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DOI：
10.1016/s1097-2765(00)80398-6
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发表时间：
2000-01-01
期刊：
影响因子：
16
通讯作者：
Anderson, RA
中科院分区：
文献类型：
--
作者：
Kunz, J;Wilson, MP;Anderson, RA
磷脂酰肌醇-4，5-二磷酸在调节细胞增殖和存活、细胞骨架重组和膜运输中起关键作用。然而，很少有人知道它的合成的时间和空间调控。高等真核细胞有可能使用两种不同的途径产生磷脂酰肌醇-4，5-二磷酸。这些途径需要两类磷脂酰肌醇磷酸激酶，称为I型和II型PIP激酶。虽然高度相关的序列，这些激酶定位于不同的亚细胞区室，磷酸化不同的底物，并在功能上是非冗余的。在这里，我们表明，一个20- 25-氨基酸环跨越催化位点，称为激活环，确定酶的特异性和亚细胞靶向PIP激酶。因此，激活环在多个水平上控制信号传导特异性和PIP激酶功能。
Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels.