EGFR endocytosis: more than meets the eye

Sapmaz, Ayşegül; Erson-Bensan, Ayşe Elif

doi:10.18632/oncotarget.28400

Oncotarget

2023

DOI: 10.18632/oncotarget.28400

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EGFR endocytosis: more than meets the eye

Ayşegül Sapmaz¹,

Ayşe Elif Erson-Bensan²

Abstract: Behind the scenes of signaling cascades initiated by activated receptors, endocytosis determines the fate of internalized proteins through degradation in lysosomes or recycling. Over the years, significant progress has been made in understanding the mechanisms of endocytosis and deregulation in disease states. Here we review the role of the EGF-SNX3-EGFR axis in breast cancers with an extended discussion on deregulated EGFR endocytosis in cancer.

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Rme-6 integrates EGFR trafficking and signalling to regulate ERK1/2 signalosome dynamics

Smythe

Alshahrani

Zhu

et al. 2023

Preprint

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Epidermal growth factor receptor (EGFR) signalling results in a variety of cell behaviours, including cell proliferation, migration and apoptosis, which depend on cell context. Here we have explored how the Rab5GEF, Rme-6, regulates EGFR signalling by modulating endocytic flux. We demonstrate that Rme-6, which acts early in the endocytic pathway, regulates EGFR trafficking through an endocytic compartment that is competent for ERK1/2 signalling. While overexpression of Rme-6 results in enhanced ERK1/2 nuclear localisation and c-Fos activation, loss of Rme-6 results in aberrant ERK1/2 signalling with increased cytoplasmic ERK1/2 phosphorylation (Thr202/Tyr204) but decreased ERK1/2 nuclear translocation and c-Fos activation, the latter leading to decreased cell proliferation. Phosphorylation of ERK1/2 by protein kinase 2 (CK2) is required for its nuclear translocation and our data support a model whereby Rme-6 provides a scaffold for a population of CK2 which is required for efficient nuclear translocation of ERK1/2. Rme-6 is itself a substrate for CK2 on Thr642 and Ser996 and phosphorylation on these sites can activate its Rab5GEF activity and endocytic trafficking of EGFR. Together our results indicate that that Rme-6 co-ordinates EGFR trafficking and signalling to regulate the assembly and disassembly of an ERK1/2 signalosome.

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Rme-6 integrates EGFR trafficking and signalling to regulate ERK1/2 signalosome dynamics

Smythe

Alshahrani

Zhu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

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EGFR endocytosis: more than meets the eye

Cited by 1 publication

References 33 publications

Rme-6 integrates EGFR trafficking and signalling to regulate ERK1/2 signalosome dynamics

Rme-6 integrates EGFR trafficking and signalling to regulate ERK1/2 signalosome dynamics

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