Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes.
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.
Krauss
Michael
M
Institute of Chemistry and Biochemistry, Department of Membrane Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
Kukhtina
Viktoria
V
Pechstein
Arndt
A
Haucke
Volker
V
D033962:Adaptor Protein Complex 2 / Q000737:chemistry*; D033983:Adaptor Protein Complex mu Subunits / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D050656:Transcription Factor AP-2 / Q000378:metabolism*
D033962:Adaptor Protein Complex 2; D033983:Adaptor Protein Complex mu Subunits; D019269:Phosphatidylinositol 4,5-Diphosphate; D020033:Protein Isoforms; D050656:Transcription Factor AP-2; C438885:adaptor protein complex 2, mu 1 subunit; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase