Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.
Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.
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DOI：
10.1038/s41467-022-34298-2
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发表时间：
2022-11-03
影响因子：
16.6
通讯作者：
Francavilla, Chiara
中科院分区：
文献类型：
--
作者：
Watson, Joanne;Ferguson, Harriet R.;Brady, Rosie M.;Ferguson, Jennifer;Fullwood, Paul;Mo, Hanyi;Bexley, Katherine H.;Knight, David;Howell, Gareth;Schwartz, Jean-Marc;Smith, Michael P.;Francavilla, Chiara
受体酪氨酸激酶（RTK）胞吞依赖性信号传导在发育和成体稳态期间驱动细胞增殖和运动，但在疾病（包括癌症）中失调。在胞吞作用期间，特别是在再循环至质膜期间，RTK信号传导伙伴的募集仍然未知。专注于成纤维细胞生长因子受体2b（FGFR2b）再循环，我们通过开发基于APEX2驱动的生物素化随后磷酸化肽富集的空间分辨磷酸蛋白质组学（SRP）方法，揭示了与再循环内体接近的FGFR信号传导伴侣。将其与传统的磷酸化蛋白质组学，生物信息学和靶向测定相结合，我们发现FGFR2b由其再循环配体FGF10刺激激活mTOR依赖性信号传导和再循环内体的ULK1，导致自噬抑制和细胞存活。这增加了RTK再循环在协调细胞命运中日益重要的作用，并表明配体响应性癌细胞中存在治疗靶向脆弱性。将SRP与其他系统生物学方法相结合，为空间解析细胞信号提供了一个强大的工具。在胞吞作用期间，特别是在再循环至质膜期间，受体酪氨酸激酶信号传导伙伴的募集对于信号传播和调节至关重要。在这里，作者用空间分辨磷酸蛋白质组学方法揭示了FGFR信号传导伙伴接近再循环内体。
Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we reveal FGFR signalling partners proximal to recycling endosomes by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphorylated peptides enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncover that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signalling and ULK1 at the recycling endosomes, leading to autophagy suppression and cell survival. This adds to the growing importance of RTK recycling in orchestrating cell fate and suggests a therapeutically targetable vulnerability in ligand-responsive cancer cells. Integrating SRP with other systems biology approaches provides a powerful tool to spatially resolve cellular signalling. Recruitment of Receptor Tyrosine Kinase signalling partners during endocytosis, specifically during recycling to the plasma membrane, is crucial to signal propagation and regulation. Here, the authors reveal FGFR signalling partners proximal to recycling endosomes with a spatially resolved phosphoproteomics approach.
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DOI：
10.1002/wdev.392
发表时间：
2021-01
期刊：
Wiley interdisciplinary reviews. Developmental biology
影响因子：
--
作者：
Bosch JA;Chen CL;Perrimon N
通讯作者：
Perrimon N
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
15.9
作者：
Chernikova, Sophia B.;Nguyen, Rochelle B.;Brown, J. Martin
通讯作者：
Brown, J. Martin
影响因子：
4.8
作者：
Dauner, Kristin;Eid, Walaa;Zha, Xiaohui
通讯作者：
Zha, Xiaohui
DOI：
10.1016/j.biocel.2014.01.009
发表时间：
2014-04-01
影响因子：
4
作者：
Barrow-McGee, Rachel;Kermorgant, Stephanie
通讯作者：
Kermorgant, Stephanie