Open AccessPhotoaffinity-engineered protein scaffold for systematically exploring native phosphotyrosine signaling complexes in tumor samples
Author(s) -
Bizhu Chu,
An He,
Yeteng Tian,
Wan He,
Peizhong Chen,
Jintao Hu,
Ruilian Xu,
Wenbin Zhou,
Mingjie Zhang,
Pengyuan Yang,
Shawn S.C. Li,
Ying Sun,
Pengfei Li,
Tony Hunter,
Ruijun Tian
Publication year - 2018
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1805633115
Subject(s) - scaffold protein , sh2 domain , pdgfrb , proteome , proteomics , signal transduction , proto oncogene tyrosine protein kinase src , chemistry , protein–protein interaction , cell signaling , biochemistry , microbiology and biotechnology , biology , gene
Significance Phosphotyrosine (pTyr)-dependent protein complexes are key machinery for regulating cancer signaling. We developed the Photo-pTyr-scaffold approach for unbiasedly capturing and exploring weak and dynamic pTyr protein complexes. By utilizing the Src kinase Src homology 2 superbinder with nanomolar binding affinity, Photo-pTyr-scaffold showed superior sensitivity for profiling native pTyr protein complexes in cancer cells and breast tumor samples. Importantly, we discovered PDGFRB to be a critical signaling node for mediating intercellular cancer signaling, which is highly expressed but independent of ERBB2, the well-established breast cancer therapeutic target. Our results could lead to new targeted therapies for breast cancer and generic approaches for exploring dynamic protein complexes related to other types of protein posttranslational modifications and discovering biomarkers readily from complex clinical samples.
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