Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.

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 wha...

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Main Authors: Jun Sung Lee, Il Shin Kim, Jung Hwan Kim, Wonhwa Cho, Pann-Ghill Suh, Sung Ho Ryu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-09-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2739277?pdf=render
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author Jun Sung Lee
Il Shin Kim
Jung Hwan Kim
Wonhwa Cho
Pann-Ghill Suh
Sung Ho Ryu
author_facet Jun Sung Lee
Il Shin Kim
Jung Hwan Kim
Wonhwa Cho
Pann-Ghill Suh
Sung Ho Ryu
author_sort Jun Sung Lee
collection DOAJ
description 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. METHODOLOGY/PRINCIPAL FINDINGS: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/SIGNIFICANCE: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.
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spelling doaj.art-c3691867e3174b27b402979cca754ffa2022-12-21T18:58:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e709010.1371/journal.pone.0007090Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.Jun Sung LeeIl Shin KimJung Hwan KimWonhwa ChoPann-Ghill SuhSung Ho RyuBACKGROUND: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. METHODOLOGY/PRINCIPAL FINDINGS: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/SIGNIFICANCE: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.http://europepmc.org/articles/PMC2739277?pdf=render
spellingShingle Jun Sung Lee
Il Shin Kim
Jung Hwan Kim
Wonhwa Cho
Pann-Ghill Suh
Sung Ho Ryu
Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
PLoS ONE
title Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
title_full Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
title_fullStr Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
title_full_unstemmed Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
title_short Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
title_sort determination of egfr endocytosis kinetic by auto regulatory association of pld1 with mu2
url http://europepmc.org/articles/PMC2739277?pdf=render
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