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Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11934-9. Epub 2006 Jul 31.

Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes.

Author information

1
Institute of Chemistry and Biochemistry, Department of Membrane Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.

Abstract

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.

PMID:
16880396
PMCID:
PMC1567676
DOI:
10.1073/pnas.0510306103
[Indexed for MEDLINE]
Free PMC Article

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