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Differential Effects of EGFR Ligands on Endocytic Sorting of the Receptor
Abstract
Endocytic downregulation is a pivotal mechanism turning off signalling from the EGF receptor (EGFR). It is well established that whereas EGF binding leads to lysosomal degradation of EGFR, transforming growth factor (TGF)‐α causes receptor recycling. TGF‐α therefore leads to continuous signalling and is a more potent mitogen than EGF. In addition to EGF and TGF‐α, five EGFR ligands have been identified. Although many of these ligands are upregulated in cancers, very little is known about their effect on EGFR trafficking. We have compared the effect of six different ligands on endocytic trafficking of EGFR. We find that, whereas they all stimulate receptor internalization, they have very diverse effects on endocytic sorting. Heparin‐binding EGF‐like growth factor and Betacellulin target all EGFRs for lysosomal degradation. In contrast, TGF‐α and epiregulin lead to complete receptor recycling. EGF leads to lysosomal degradation of the majority but not all EGFRs. Amphiregulin does not target EGFR for lysosomal degradation but causes fast as well as slow EGFR recycling. The Cbl ubiquitin ligases, especially c‐Cbl, are responsible for EGFR ubiquitination after stimulation with all ligands, and persistent EGFR phosphorylation and ubiquitination largely correlate with receptor degradation.
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Postactivation endocytic trafficking of EGFR has been well elucidated.
“While postactivation endocytic trafficking of EGFR has been well elucidated, little is known about mechanisms of basal/preactivation surface display of EGFR.”
From EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling (2020) · cites this paper as [11]
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Tom, E. C., Mushtaq, I., Mohapatra, B. C., Luan, H., Bhat, A. M., Zutshi, N., Chakraborty, S., Islam, N., Arya, P., Bielecki, T. A., et al. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00434-19 · Cited by 13
Metadata
- Authors
- Roepstorff, K., Grandal, M. V., Henriksen, L., Knudsen, S. L. J., Lerdrup, M., Grøvdal, L., Willumsen, B. M., & Van Deurs, B.
- Venue
- Traffic
- Publisher
- Wiley
- Published
- 2009-07-02
- Volume
- 10
- Issue
- 8
- Pages
- 1115-1127
- ISSN
- 1398-9219
- 1600-0854
- PMC
- PMC2723868
- Cited by
- 310
- References
- 1
- Language
- en
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