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...
Main Authors: | , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2009-09-01
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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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format | Article |
id | doaj.art-c3691867e3174b27b402979cca754ffa |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-21T15:58:40Z |
publishDate | 2009-09-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
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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