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Updated: Jun 15, 2026
Identification of Rare Antigen-Specific T Cells from Mouse Lungs with Peptide:Major Histocompatibility Complex Tetramers
Published on: July 19, 2024
A chemical and phosphoproteomic characterization of dasatinib action in lung cancer
Jiannong Li1, Uwe Rix, Bin Fang
1Department of Thoracic Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Abstract:
We describe a strategy for comprehending signaling pathways that are active in lung cancer cells and that are targeted by dasatinib using chemical proteomics to identify direct interacting proteins combined with immunoaffinity purification of tyrosine-phosphorylated peptides corresponding to activated tyrosine kinases. We identified nearly 40 different kinase targets of dasatinib. These include SRC-family kinase (SFK) members (LYN, SRC, FYN, LCK and YES), nonreceptor tyrosine kinases (FRK, BRK and ACK) and receptor tyrosine kinases (Ephrin receptors, DDR1 and EGFR). Using quantitative phosphoproteomics, we identified peptides corresponding to autophosphorylation sites of these tyrosine kinases that are inhibited in a concentration-dependent manner by dasatinib. Using drug-resistant gatekeeper mutants, we show that SFKs (particularly SRC and FYN), as well as EGFR, are relevant targets for dasatinib action. The combined mass spectrometry-based approach described here provides a system-level view of dasatinib action in cancer cells and suggests both functional targets and a rationale for combinatorial therapeutic strategies.
Insights
This study reveals nearly 40 kinase targets of dasatinib in lung cancer cells, including SRC-family kinases and EGFR, using chemical proteomics. These findings offer insights into dasatinib
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Lung cancer involves complex signaling pathways.
- Dasatinib is a tyrosine kinase inhibitor used in cancer therapy.
- Understanding dasatinib's precise targets is crucial for optimizing treatment.
Purpose of the Study:
- To comprehensively identify direct protein targets of dasatinib in lung cancer cells.
- To elucidate the signaling pathways affected by dasatinib.
- To provide a systems-level understanding of dasatinib's mechanism of action.
Main Methods:
- Utilized chemical proteomics to identify direct protein interactors of dasatinib.
- Employed immunoaffinity purification of tyrosine-phosphorylated peptides.
- Applied quantitative phosphoproteomics and drug-resistant gatekeeper mutants.
Main Results:
- Identified approximately 40 kinase targets of dasatinib, including SRC-family kinases (SFKs) and receptor tyrosine kinases (e.g., EGFR).
- Demonstrated concentration-dependent inhibition of tyrosine kinase autophosphorylation sites by dasatinib.
- Confirmed SFKs (SRC, FYN) and EGFR as relevant targets through drug-resistant mutant studies.
Conclusions:
- The described mass spectrometry-based approach provides a systems-level view of dasatinib's action.
- Identified key functional targets of dasatinib in lung cancer.
- Suggests a rationale for developing combinatorial therapeutic strategies targeting these kinases.
