High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways.
Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathwa...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3018525?pdf=render |
| _version_ | 1819087823563653120 |
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| author | Jordan A Krall Elsa M Beyer Gavin MacBeath |
| author_facet | Jordan A Krall Elsa M Beyer Gavin MacBeath |
| author_sort | Jordan A Krall |
| collection | DOAJ |
| description | Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways. |
| first_indexed | 2024-12-21T21:42:16Z |
| format | Article |
| id | doaj.art-df9034c0518342f0b38a446f1a93a58d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T21:42:16Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-df9034c0518342f0b38a446f1a93a58d2022-12-21T18:49:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1594510.1371/journal.pone.0015945High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways.Jordan A KrallElsa M BeyerGavin MacBeathSignaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways.http://europepmc.org/articles/PMC3018525?pdf=render |
| spellingShingle | Jordan A Krall Elsa M Beyer Gavin MacBeath High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. PLoS ONE |
| title | High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. |
| title_full | High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. |
| title_fullStr | High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. |
| title_full_unstemmed | High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. |
| title_short | High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. |
| title_sort | high and low affinity epidermal growth factor receptor ligand interactions activate distinct signaling pathways |
| url | http://europepmc.org/articles/PMC3018525?pdf=render |
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