Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2μ–cargo complexes
- 8 August 2006
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 103 (32) , 11934-11939
- https://doi.org/10.1073/pnas.0510306103
Abstract
Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] 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)P2 synthesis. AP-2 directly interacts with the kinase core domain of type I PIPK isozymes via its μ2-subunit in vitro and in native protein extracts. Endocytic cargo protein binding to μ2 leads to a potent stimulation of PIPK activity. These data thus identify a positive feedback loop consisting of endocytic cargo proteins, AP-2μ, and PIPK type I which may provide a specific pool of PI(4,5)P2 dedicated to clathrin/AP-2-dependent receptor internalization.Keywords
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