title: Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
abstract: BACKGROUND
  Upon ligand binding, cell surface signaling receptors are internalized through a process tightly regulated by endocytic proteins and adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities and roles of endocytic proteins are becoming clearer, it is still unclear what determines the receptor endocytosis kinetics which is mainly regulated by the accumulation of endocytic apparatus to the activated receptors.
  
  
  RESULTS
  Here we employed the kinetic analysis of endocytosis and adaptor recruitment to show that mu2, a subunit of AP2 interacts directly with phospholipase D (PLD)1, a receptor-associated signaling protein and this facilitates the membrane recruitment of AP2 and the endocytosis of epidermal growth factor receptor (EGFR). We also demonstrate that the PLD1-mu2 interaction requires the binding of PLD1 with phosphatidic acid, its own product.
  
  
  CONCLUSIONS
  These results suggest that the temporal regulation of EGFR endocytosis is achieved by auto-regulatory PLD1 which senses the receptor activation and triggers the translocation of AP2 near to the activated receptor.
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Il Shin
authors.initials: IS
authors.lastname: Kim
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Cho
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism*; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D033962:Adaptor Protein Complex 2; D033983:Adaptor Protein Complex mu Subunits; D008024:Ligands; D010712:Phosphatidic Acids; C438886:adaptor protein complex 2, mu 2 subunit; D005982:Glutathione Transferase; D066246:ErbB Receptors; D010739:Phospholipase D; C106801:phospholipase D1