دورية أكاديمية
Oncogenic Mutations Rewire Signaling Pathways by Switching Protein Recruitment to Phosphotyrosine Sites.
| العنوان: | Oncogenic Mutations Rewire Signaling Pathways by Switching Protein Recruitment to Phosphotyrosine Sites. |
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| المؤلفون: | Lundby A; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: alicia.lundby@sund.ku.dk., Franciosa G; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Emdal KB; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Refsgaard JC; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Gnosa SP; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Bekker-Jensen DB; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Secher A; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark; Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark., Maurya SR; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Paul I; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Mendez BL; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Kelstrup CD; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Francavilla C; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Kveiborg M; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Montoya G; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Jensen LJ; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark., Olsen JV; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark. Electronic address: jesper.olsen@cpr.ku.dk. |
| المصدر: | Cell [Cell] 2019 Oct 03; Vol. 179 (2), pp. 543-560.e26. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| مواضيع طبية MeSH: | Carcinogenesis/*genetics , ErbB Receptors/*genetics , Lung Neoplasms/*genetics , Lung Neoplasms/*metabolism , Phosphotyrosine/*metabolism, A549 Cells ; Animals ; Humans ; Mass Spectrometry/methods ; Mutation ; Phosphoproteins/metabolism ; Phosphorylation ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Zebrafish |
| مستخلص: | Tyrosine phosphorylation regulates multi-layered signaling networks with broad implications in (patho)physiology, but high-throughput methods for functional annotation of phosphotyrosine sites are lacking. To decipher phosphotyrosine signaling directly in tissue samples, we developed a mass-spectrometry-based interaction proteomics approach. We measured the in vivo EGF-dependent signaling network in lung tissue quantifying >1,000 phosphotyrosine sites. To assign function to all EGF-regulated sites, we determined their recruited protein signaling complexes in lung tissue by interaction proteomics. We demonstrated how mutations near tyrosine residues introduce molecular switches that rewire cancer signaling networks, and we revealed oncogenic properties of such a lung cancer EGFR mutant. To demonstrate the scalability of the approach, we performed >1,000 phosphopeptide pulldowns and analyzed them by rapid mass spectrometric analysis, revealing tissue-specific differences in interactors. Our approach is a general strategy for functional annotation of phosphorylation sites in tissues, enabling in-depth mechanistic insights into oncogenic rewiring of signaling networks. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: EGFR; SH2; cancer signaling; interaction proteomics; mass spectrometry; peptide pulldown; phosphopeptides; phosphoproteomics; phosphotyrosine; zebrafish |
| المشرفين على المادة: | 0 (Phosphoproteins) 21820-51-9 (Phosphotyrosine) EC 2.7.10.1 (ErbB Receptors) |
| تواريخ الأحداث: | Date Created: 20191005 Date Completed: 20200609 Latest Revision: 20200609 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.cell.2019.09.008 |
| PMID: | 31585087 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4172 |
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| DOI: | 10.1016/j.cell.2019.09.008 |