@article{b17f80a39dbd41b1900c7af5a6eff1e7,
title = "Reciprocal Priming between Receptor Tyrosine Kinases at Recycling Endosomes Orchestrates Cellular Signalling Outputs",
abstract = "Integration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains poorly elucidated. Combining quantitative phosphoproteomics and targeted assays, we generated a detailed picture of recycling-dependent fibroblast growth factor (FGF) signalling in breast cancer cells, with a focus on distinct FGF receptors (FGFRs). We discovered reciprocal priming between FGFRs and epidermal growth factor (EGF) receptor (EGFR) that is coordinated at recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR-mediated proliferation but not cell invasion. In turn, FGFR signalling primes EGFmediated outputs via EGFR threonine 693 phosphorylation. This reciprocal priming between distinct families of RTKs from recycling endosomes exemplifies a novel signalling integration hub where recycling endosomes orchestrate cellular behaviour. Therefore, targeting reciprocal priming over individual receptors may improve personalized therapies in breast and other cancers.",
keywords = "fibroblast growth factor receptor, quantitative phosphoproteomics, receptor tyrosine kinases, signalling, trafficking",
author = "Michael Smith and Harriet Ferguson and Jennnifer Ferguson and Egor Zindy and Katarzyna Kowalczyk and Thomas Kedward and Christian Bates and Joseph Parsons and Joanne Watson and Sarah Chandler and Paul Fullwood and Stacey Warwood and Robert Clarke and Chiara Francavilla",
note = "Funding Information: We thank Profs. Lowe and Woodman, and Drs Caswell, Tournier and Lopez-Castejon for reading the manuscript and the Bioimaging and the Bio-MS Facilities (University of Manchester). Research in CF lab is supported by Wellcome Trust (WT Sir Henry Dale fellowship 107636/Z/15/Z), the Biotechnology and Biological Sciences Research Council (BB/R015864/1), and Medical Research Council (MR/T016043/1). PhD students are supported by BBSRC Doctoral Training Programme (HF and JW: BB/M011208/1); Wellcome Trust (CB: 210002/Z/17/Z); CR-UK Non-Clinical Training Award (JP: A27445); and NIHR Manchester Biomedical Research Centre non-clinical PhD Studentship (TK: IS-BRC-1215-20007). RBC is supported by Cancer Research UK and Breast Cancer Now (MAN-Q2-Y4/5). Funding Information: We thank Profs. Lowe and Woodman, and Drs Caswell, Tournier and Lopez‐Castejon for reading the manuscript and the Bioimaging and the Bio‐MS Facilities (University of Manchester). Research in CF lab is supported by Wellcome Trust (WT Sir Henry Dale fellowship 107636/Z/15/Z), the Biotechnology and Biological Sciences Research Council (BB/R015864/1), and Medical Research Council (MR/T016043/1). PhD students are supported by BBSRC Doctoral Training Programme (HF and JW: BB/M011208/1); Wellcome Trust (CB: 210002/Z/17/Z); CR‐UK Non‐Clinical Training Award (JP: A27445); and NIHR Manchester Biomedical Research Centre non‐clinical PhD Studentship (TK: IS‐BRC‐1215‐20007). RBC is supported by Cancer Research UK and Breast Cancer Now (MAN‐Q2‐Y4/5). Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2021",
month = apr,
day = "28",
doi = "10.15252/embj.2020107182",
language = "English",
volume = "40",
pages = "e107182",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Springer Nature",
number = "14",
}