Krauss Michael, Kukhtina Viktoria, Pechstein Arndt, Haucke Volker
Institute of Chemistry and Biochemistry, Department of Membrane Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11934-9. doi: 10.1073/pnas.0510306103. Epub 2006 Jul 31.
Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P(2)] is an important factor for a variety of cellular functions ranging from cell signaling to actin cytoskeletal dynamics and endocytic membrane traffic. Here, we have identified the clathrin adaptor complex AP-2 as a regulator of phosphatidylinositol 4-phosphate 5-kinase (PIPK)-mediated PI(4,5)P(2) synthesis. AP-2 directly interacts with the kinase core domain of type I PIPK isozymes via its mu2-subunit in vitro and in native protein extracts. Endocytic cargo protein binding to mu2 leads to a potent stimulation of PIPK activity. These data thus identify a positive feedback loop consisting of endocytic cargo proteins, AP-2mu, and PIPK type I which may provide a specific pool of PI(4,5)P(2) dedicated to clathrin/AP-2-dependent receptor internalization.
磷脂酰肌醇（4,5）-二磷酸[PI(4,5)P₂]是多种细胞功能的重要因素，这些功能涵盖从细胞信号传导到肌动蛋白细胞骨架动力学以及内吞膜运输等各个方面。在此，我们已确定网格蛋白衔接复合体AP-2是磷脂酰肌醇4-磷酸5-激酶（PIPK）介导的PI(4,5)P₂合成的调节因子。在体外和天然蛋白质提取物中，AP-2通过其μ2亚基直接与I型PIPK同工酶的激酶核心结构域相互作用。内吞货物蛋白与μ2的结合会强力刺激PIPK活性。因此，这些数据确定了一个由内吞货物蛋白、AP-2μ和I型PIPK组成的正反馈回路，该回路可能提供专门用于网格蛋白/AP-2依赖性受体内化的特定PI(4,5)P₂池。
