ArticleProceedings of the National Academy of Sciences of the United States of America2018
Photoaffinity-engineered protein scaffold for systematically exploring native phosphotyrosine signaling complexes in tumor samples.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Branching beyond bifunctional linkers: synthesis of macrocyclic and trivalent PROTACs.Nature protocols · 2026Review
- Phosphorylation of tumour suppressor Amotl2 by IKBKE kinase promotes YAP1 signalling, enhancing glioblastoma growth.Frontiers in oncology · 2026Article
- Article
- [Applications of high performance liquid chromatography-mass spectrometry in proteomics].Se pu = Chinese journal of chromatography · 2024Review
- Novel dual inhibitors of PARP and HDAC induce intratumoral STING-mediated antitumor immunity in triple-negative breast cancer.Cell death & disease · 2024Article
- Chemical biology tools for protein labelling: insights into cell-cell communication.The Biochemical journal · 2023Review
- Deciphering intercellular signaling complexes by interaction-guided chemical proteomics.Nature communications · 2023Article
- Functional and Clinical Proteomic Exploration of Pancreatic Cancer.Molecular & cellular proteomics : MCP · 2023Review
- Kindlin-2 promotes Src-mediated tyrosine phosphorylation of androgen receptor and contributes to breast cancer progression.Cell death & disease · 2022Article
- [Advances in high-throughput proteomic analysis].Se pu = Chinese journal of chromatography · 2021Review
- Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability.Oncogenesis · 2020Article
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
Phosphotyrosine (pTyr)-regulated protein complexes play critical roles in cancer signaling. The systematic characterization of these protein complexes in tumor samples remains a challenge due to their limited access and the transient nature of pTyr-mediated interactions. We developed a hybrid chemical proteomics approach, termed Photo-pTyr-scaffold, by engineering Src homology 2 (SH2) domains, which specifically bind pTyr proteins, with both trifunctional chemical probes and genetic mutations to overcome these challenges. Dynamic SH2 domain-scaffolding protein complexes were efficiently cross-linked under mild UV light, captured by biotin tag, and identified by mass spectrometry. This approach was successfully used to profile native pTyr protein complexes from breast cancer tissue samples on a proteome scale with high selectivity, achieving about 100 times higher sensitivity for detecting pTyr signaling proteins than that afforded by traditional immunohistochemical methods. Among more than 1,000 identified pTyr proteins, receptor tyrosine kinase PDGFRB expressed on cancer-associated fibroblasts was validated as an important intercellular signaling regulator with poor expression correlation to ERBB2, and blockade of PDGFRB signaling could efficiently suppress tumor growth. The Photo-pTyr-scaffold approach may become a generic tool for readily profiling dynamic pTyr signaling complexes in clinically relevant samples.
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