ArticleMolecular & cellular proteomics : MCP2012
Temporal profiling of lapatinib-suppressed phosphorylation signals in EGFR/HER2 pathways.
Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 56 citations in OpenAlex.
- Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy.Clinical proteomics · 2026Article
- BDDN: bayesian dynamic differential network analysis in cancer proteomics.BMC bioinformatics · 2026Article
- Phosphoproteomic analysis reveals the diversity of signaling behind ErbB-inhibitor-induced phenotypes.The FEBS journal · 2025Article
- Phosphorylation regulates the chromatin remodeler SMARCAD1 in nucleosome binding, ATP hydrolysis, and histone exchange.The Journal of biological chemistry · 2024Article
- Validity of the cell-extracted proteome as a substrate pool for exploring phosphorylation motifs of kinases.Genes to cells : devoted to molecular & cellular mechanisms · 2023Article
- MAVEN: compound mechanism of action analysis and visualisation using transcriptomics and compound structure data in R/Shiny.BMC bioinformatics · 2023Article
- A Novel ERK2 Degrader Z734 Induces Apoptosis of MCF-7 Cells via the HERC3/p53 Signaling Pathway.Molecules (Basel, Switzerland) · 2022Article
- Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma.Frontiers in oncology · 2021Article
- Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies.Scientific reports · 2020Article
- Regulation of eukaryotic translation initiation factor 6 dynamics through multisite phosphorylation by GSK3.The Journal of biological chemistry · 2020Article
- Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.Cellular and molecular life sciences : CMLS · 2020Review
- Monitoring protein communities and their responses to therapeutics.Nature reviews. Drug discovery · 2020Review
- A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies.Cancer chemotherapy and pharmacology · 2019Article
- Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.The Journal of biological chemistry · 2019Article
- A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.Frontiers in endocrinology · 2018Article
- Reversible phosphorylation of the 26S proteasome.Protein & cell · 2017Review
- Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer.Scientific reports · 2017Article
- Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells.Oncotarget · 2016Article
- Integrating proteomics with electrochemistry for identifying kinase biomarkers.Chemical science · 2015Article
- The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.Journal of mammary gland biology and neoplasia · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lapatinib is a clinically potent kinase inhibitor for breast cancer patients because of its outstanding selectivity for epidermal growth factor receptor (EGFR) and EGFR2 (also known as HER2). However, there is only limited information about the in vivo effects of lapatinib on EGFR/HER2 and downstream signaling targets. Here, we profiled the lapatinib-induced time- and dose-dependent phosphorylation dynamics in SKBR3 breast cancer cells by means of quantitative phosphoproteomics. Among 4953 identified phosphopeptides from 1548 proteins, a small proportion (5-7%) was regulated at least twofold by 1-10 μm lapatinib. We obtained a comprehensive phosphorylation map of 21 sites on EGFR/HER2, including nine novel sites on HER2. Among them, serine/threonine phosphosites located in a small region of HER2 (amino acid residues 1049-1083) were up-regulated by the drug, whereas all other sites were down-regulated. We show that cAMP-dependent protein kinase is involved in phosphorylation of this particular region of HER2 and regulates HER2 tyrosine kinase activity. Computational analyses of quantitative phosphoproteome data indicated for the first time that protein-protein networks related to cytoskeletal organization and transcriptional/translational regulation, such as RNP complexes (i.e. hnRNP, snRNP, telomerase, ribosome), are linked to EGFR/HER2 signaling networks. To our knowledge, this is the first report to profile the temporal response of phosphorylation dynamics to a kinase inhibitor. The results provide new insights into EGFR/HER2 regulation through region-specific phosphorylation, as well as a global view of the cellular signaling networks associated with the anti-breast cancer action of lapatinib.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.