ArticleScience signaling2011
Global phosphoproteomics reveals crosstalk between Bcr-Abl and negative feedback mechanisms controlling Src signaling.
Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- The R451 site is critical for PTPN18 to exert tumor suppressive effects in breast cancer through the negative regulatory interacting protein fibrillarin.Cell death & disease · 2026Article
- Deep Learning in Phosphoproteomics: Methods and Application in Cancer Drug Discovery.Proteomes · 2023Review
- The Activity of Novel BCR-ABL Small-Molecule Degraders Containing Pyrimidine Rings and Their Role in Overcoming Drug Resistance.Journal of oncology · 2022Article
- PTPN18 Stimulates the Development of Ovarian Cancer by Activating the PI3K/AKT Signaling.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- BCR-ABL induces tyrosine phosphorylation of YAP leading to expression of Survivin and Cyclin D1 in chronic myeloid leukemia cells.International journal of hematology · 2019Article
- High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network.Molecular systems biology · 2019Article
- Phosphopeptide Enrichment Coupled with Label-free Quantitative Mass Spectrometry to Investigate the Phosphoproteome in Prostate Cancer.Journal of visualized experiments : JoVE · 2018Article
- Polypharmacology-based ceritinib repurposing using integrated functional proteomics.Nature chemical biology · 2017Article
- Csk-homologous kinase (Chk) is an efficient inhibitor of Src-family kinases but a poor catalyst of phosphorylation of their C-terminal regulatory tyrosine.Cell communication and signaling : CCS · 2017Article
- Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis.Leukemia · 2017Article
- Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics.Leukemia · 2017Article
- Quantitative phosphotyrosine profiling of patient-derived xenografts identifies therapeutic targets in pediatric leukemia.Cancer research · 2016Article
- JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma.Cell discovery · 2016Article
- Protein networks and activation of lymphocytes.Current opinion in immunology · 2015Review
- Neuroblastoma tyrosine kinase signaling networks involve FYN and LYN in endosomes and lipid rafts.PLoS computational biology · 2015Article
- Analytical challenges translating mass spectrometry-based phosphoproteomics from discovery to clinical applications.Electrophoresis · 2014Review
- microRNA expression signatures of gastrointestinal stromal tumours: associations with imatinib resistance and patient outcome.British journal of cancer · 2014Article
- Quantitative analysis of signaling networks across differentially embedded tumors highlights interpatient heterogeneity in human glioblastoma.Journal of proteome research · 2014Article
- Proteomics for systems toxicology.Computational and structural biotechnology journal · 2014Review
- Complexity of metastasis-associated SDF-1 ligand signaling in breast cancer stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
In subtypes and late stages of leukemias driven by the tyrosine kinase fusion protein Bcr-Abl, signaling by the Src family kinases (SFKs) critically contributes to the leukemic phenotype. We performed global tyrosine phosphoprofiling by quantitative mass spectrometry of Bcr-Abl-transformed cells in which the activities of the SFKs were perturbed to build a detailed context-dependent network of cancer signaling. Perturbation of the SFKs Lyn and Hck with genetics or inhibitors revealed Bcr-Abl downstream phosphorylation events either mediated by or independent of SFKs. We identified multiple negative feedback mechanisms within the network of signaling events affected by Bcr-Abl and SFKs and found that Bcr-Abl attenuated these inhibitory mechanisms. The C-terminal Src kinase (Csk)-binding protein Pag1 (also known as Cbp) and the tyrosine phosphatase Ptpn18 both mediated negative feedback to SFKs. We observed Bcr-Abl-mediated phosphorylation of the phosphatase Shp2 (Ptpn11), and this may contribute to the suppression of these negative feedback mechanisms to promote Bcr-Abl-activated SFK signaling. Csk and a kinase-deficient Csk mutant both produced similar globally repressive signaling consequences, suggesting a critical role for the adaptor protein function of Csk in its inhibition of Bcr-Abl and SFK signaling. The identified Bcr-Abl-activated SFK regulatory mechanisms are candidates for dysregulation during leukemia progression and acquisition of SFK-mediated drug resistance.
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