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Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2
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 wh...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739277/ https://www.ncbi.nlm.nih.gov/pubmed/19763255 http://dx.doi.org/10.1371/journal.pone.0007090 |
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author | Lee, Jun Sung Kim, Il Shin Kim, Jung Hwan Cho, Wonhwa Suh, Pann-Ghill Ryu, Sung Ho |
author_facet | Lee, Jun Sung Kim, Il Shin Kim, Jung Hwan Cho, Wonhwa Suh, Pann-Ghill Ryu, Sung Ho |
author_sort | Lee, Jun Sung |
collection | PubMed |
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 μ2, 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-μ2 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. |
format | Text |
id | pubmed-2739277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27392772009-09-18 Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 Lee, Jun Sung Kim, Il Shin Kim, Jung Hwan Cho, Wonhwa Suh, Pann-Ghill Ryu, Sung Ho PLoS One Research Article 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 μ2, 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-μ2 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. Public Library of Science 2009-09-18 /pmc/articles/PMC2739277/ /pubmed/19763255 http://dx.doi.org/10.1371/journal.pone.0007090 Text en Lee et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lee, Jun Sung Kim, Il Shin Kim, Jung Hwan Cho, Wonhwa Suh, Pann-Ghill Ryu, Sung Ho Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 |
title | Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 |
title_full | Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 |
title_fullStr | Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 |
title_full_unstemmed | Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 |
title_short | Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 |
title_sort | determination of egfr endocytosis kinetic by auto-regulatory association of pld1 with μ2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739277/ https://www.ncbi.nlm.nih.gov/pubmed/19763255 http://dx.doi.org/10.1371/journal.pone.0007090 |
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