Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking
| Autor: | Giuseppe Cazzamali, Blagoy Blagoev, Jón Otti Sigurdsson, Jesper V. Olsen, Chiara Francavilla, Anna-Kathrine Pedersen, Kristoffer T.G. Rigbolt, Gopal Karemore, Moreno Papetti |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Proteomics Interactome Receptor tyrosine kinase 03 medical and health sciences Structural Biology Epidermal growth factor Cell Movement Cell Line Tumor Functional selectivity Humans Epidermal growth factor receptor Protein Interaction Maps Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Cell Proliferation biology Epidermal Growth Factor Chemistry Membrane Proteins rab7 GTP-Binding Proteins Transforming Growth Factor alpha Cell biology ErbB Receptors Protein Transport 030104 developmental biology rab GTP-Binding Proteins Proteolysis biology.protein Signal transduction HeLa Cells Signal Transduction |
| Zdroj: | Francavilla, C, Papetti, M, Rigbolt, K T G, Pedersen, A-K, Sigurdsson, J O, Cazzamali, G, Karemore, G, Blagoev, B & Olsen, J V 2016, ' Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking ', Nature Structural and Molecular Biology, vol. 23, no. 6, pp. 608–618 . https://doi.org/10.1038/nsmb.3218 Francavilla, C, Papetti, M, Rigbolt, K T G, Pedersen, A-K, Sigurdsson, J O, Cazzamali, G, Karemore, G, Blagoev, B & Olsen, J V 2016, ' Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking ', Nature Structural and Molecular Biology, vol. 23, pp. 608-618 . https://doi.org/10.1038/nsmb.3218 Nature Structural & Molecular Biology Francavilla, C, Papetti, M, Rigbolt, K T G, Pedersen, A-K, Sigurdsson, J O, Cazzamali, G, Karemore, G, Blagoev, B & Olsen, J V 2016, ' Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking ', Nature Structural and Molecular Biology, vol. 23, no. 6, pp. 608-18 . https://doi.org/10.1038/nsmb.3218 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.3218 |
| Popis: | A fascinating conundrum in cell signaling is how stimulation of the same receptor tyrosine kinase with distinct ligands generates specific outcomes. To decipher the functional selectivity of EGF and TGF-α, which induce epidermal growth factor receptor (EGFR) degradation and recycling, respectively, we devised an integrated multilayered proteomics approach (IMPA). We analyzed dynamic changes in the receptor interactome, ubiquitinome, phosphoproteome, and late proteome in response to both ligands in human cells by quantitative MS and identified 67 proteins regulated at multiple levels. We identified RAB7 phosphorylation and RCP recruitment to EGFR as switches for EGF and TGF-α outputs, controlling receptor trafficking, signaling duration, proliferation, and migration. By manipulating RCP levels or phosphorylation of RAB7 in EGFR-positive cancer cells, we were able to switch a TGF-α-mediated response to an EGF-like response or vice versa as EGFR trafficking was rerouted. We propose IMPA as an approach to uncover fine-tuned regulatory mechanisms in cell signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|