Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking

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Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking. / Francavilla, Chiara; Papetti, Moreno; Rigbolt, Kristoffer T G; Pedersen, Anna-Kathrine; Sigurdsson, Jon O; Cazzamali, Giuseppe; Karemore, Gopal; Blagoev, Blagoy; Olsen, Jesper V.

I: Nature Structural and Molecular Biology, Bind 23, Nr. 6, 06.2016, s. 608–618.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Francavilla, C, Papetti, M, Rigbolt, KTG, Pedersen, A-K, Sigurdsson, JO, Cazzamali, G, Karemore, G, Blagoev, B & Olsen, JV 2016, 'Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking', Nature Structural and Molecular Biology, bind 23, nr. 6, s. 608–618. https://doi.org/10.1038/nsmb.3218

APA

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, 23(6), 608–618. https://doi.org/10.1038/nsmb.3218

Vancouver

Francavilla C, Papetti M, Rigbolt KTG, Pedersen A-K, Sigurdsson JO, Cazzamali G o.a. Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking. Nature Structural and Molecular Biology. 2016 jun.;23(6):608–618. https://doi.org/10.1038/nsmb.3218

Author

Francavilla, Chiara ; Papetti, Moreno ; Rigbolt, Kristoffer T G ; Pedersen, Anna-Kathrine ; Sigurdsson, Jon O ; Cazzamali, Giuseppe ; Karemore, Gopal ; Blagoev, Blagoy ; Olsen, Jesper V. / Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking. I: Nature Structural and Molecular Biology. 2016 ; Bind 23, Nr. 6. s. 608–618.

Bibtex

@article{704a460f9a4d4d29b8ea48b1fffd88ac,
title = "Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking",
abstract = "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.",
author = "Chiara Francavilla and Moreno Papetti and Rigbolt, {Kristoffer T G} and Anna-Kathrine Pedersen and Sigurdsson, {Jon O} and Giuseppe Cazzamali and Gopal Karemore and Blagoy Blagoev and Olsen, {Jesper V}",
year = "2016",
month = jun,
doi = "10.1038/nsmb.3218",
language = "English",
volume = "23",
pages = "608–618",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",
number = "6",

}

RIS

TY - JOUR

T1 - Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking

AU - Francavilla, Chiara

AU - Papetti, Moreno

AU - Rigbolt, Kristoffer T G

AU - Pedersen, Anna-Kathrine

AU - Sigurdsson, Jon O

AU - Cazzamali, Giuseppe

AU - Karemore, Gopal

AU - Blagoev, Blagoy

AU - Olsen, Jesper V

PY - 2016/6

Y1 - 2016/6

N2 - 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.

AB - 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.

U2 - 10.1038/nsmb.3218

DO - 10.1038/nsmb.3218

M3 - Journal article

C2 - 27136326

VL - 23

SP - 608

EP - 618

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 6

ER -

ID: 161041804