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Phosphoproteome analysis of signaling by ErbB2 in ovarian cancer cell line(1st approach)

ABSTRACT: The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals through ErbB2 are transduced is well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 using affinity chromatography and nano-LC ESI MS/MS

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Sidhanth Jayprakash

LAB HEAD: Dr.T.S. Ganesan

PROVIDER: PXD018046 | Pride | 2025-12-29

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	A_EGF.RAW	Raw
	A_EGF.mzid.gz	Mzid
	A_Lapatinib.RAW	Raw
	A_Lapatinib.mzid.gz	Mzid
	A_Starved.RAW	Raw

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Publications

Phosphoproteomic analysis reveals the diversity of signaling behind ErbB-inhibitor-induced phenotypes.

Vaparanta Katri K Song Zejia Z Farahani Iman I Jokilammi Anne A Merilahti Johannes J Örling Johanna J Virtanen Noora N Haapaniemi Pekka P Sahlgren Cecilia C Elenius Klaus K Paatero Ilkka I

The FEBS journal 20250724 24

The impact of kinase inhibitors on the phosphoproteome has been rarely investigated at a whole-organism level. Here, we performed a phosphoproteomic analysis in embryonic zebrafish to identify the signaling pathways perturbed by ErbB receptor tyrosine-protein kinase inhibitors gefitinib, lapatinib, and AG1478 at the organism level. The phosphorylation of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), Notch, Hippo ...[more]

PMID: 40705969

Similar Datasets

Phosphoproteome analysis of signaling by ErbB2 in ovarian cancer cell line (2nd approach)

Project description:The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals through ErbB2 are transduced is well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 using TIO2 and nano-LC-ESI MS/MS

2025-12-29 | PXD017985 | Pride

RNA-seq analysis of the fungal mycelium of the plant pathogen Pyricularia oryzae treated with and antimicrobial peptide analog of a Trichoderma peptaibol

Project description:We aimed at investigating the mode of action of an antimicrobial peptide analog of a Trichoderma peptaibol. Conidia of P. oryzae (IT10 strain) were cultured in Complete Medium at a final concentration of 2x105 conidia per mL for 3 days at 30 °C under shaking at 150 rpm. After three days, 50 µM of the Peptide 4rink were added to samples containing actively growing mycelium. Untreated samples were used as control. Three h after peptide treatment, fungal mycelia were collected, filtered with 100 µm Cell Strainer (Corning®), rinsed with sterile water and stored at -80 °C for RNA extraction. Total RNA was extracted with the RNeasy Plant Mini kit (Qiagen) following the manufacturer’s instructions, performing the DNase digestion directly on the column. The integrity and concentration of the RNA samples were checked with Qubit fluorimeter and Bioanalyzer. RNA samples with RIN values < 7 were discarded. Four biological replicates of each treatment were submitted to RNA sequencing and analysis at CRIBI Biotechnology Center (University of Padova). Two µg of total RNA were subjected to PolyA tail capture and rRNA depletion for selection of mRNA. Directional (stranded) RNA libraries were prepared, quantified and subjected to quality control. Sequencing was performed on Illumina Nova Seq 6000 platform. Twenty million reads were produced for each sample and checked for quality control. Based on our RNA-seq data, the molecular mechanisms of the fungicidal activity of these peptide analogs appear to be related to their ability to cause cell wall and membrane damages and to induce autophagic cell death in fungal cells. This is the first transcriptomic analysis on a fungus treated with peptaibol analogs.

2021-10-08 | E-MTAB-10927 | biostudies-arrayexpress

Phosphorylation patterns on the c-terminal tail of the angiotensin II type 1 receptor encode differential signaling pathways

Project description:Structural studies have recently shown that mechanism of selective AT1R activation by different classes of ligands is initiated by the ability of ligands to stabilize unique active conformations of the receptor. Active conformations enhance transducer coupling leading to effector mediated signaling, that has been proposed to be linked to differential phosphorylation of the c-terminal tail of the receptor. To determine how different classes of AT1R ligands effect receptor phosphorylation and activation of downstream signaling we used TMT-MS to identify the amino acid residues of the AT1R phosphorylated following treatment with the full balanced agonist Angiotensin II and a β-arrestin biased ligand, TRV023. Here we show that Ang and TRV 023 induce two distinct patterns of phosphorylation clusters a.a. residues along the entire c-tail with AngII inducing a greater magnitude than the β-arrestin biased ligand TRV 023, particularly in the proximal part of the tail. Selective mutagenesis of Ser and Thr residues, we found that of the 12 Ser/Thr residues within the c-tail, only the 4 proximal and 4 middle residues are all required for full β -arrestin functionality in response to either a balanced or β-arrestin-based ligand. Surprisingly, phosphorylation of 4 residues in the proximal c-tail is necessary for maximal G-protein activation to a full agonist. Taken together our data demonstrate that a AT1R ligands that stabilize different active confirmations of the receptor (full agonist vs. β-arrestin biased) induce distinct phosphorylation patterns on the c-tail of the receptor to evoke distinct receptor-transducer engagement and downstream receptor trafficking and signaling.

2024-07-15 | PXD032672 | Pride

Trastuzumab modulates the protein cargo of extracellular vesicles released by ERBB2+ breast cancer cells

Project description:Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is a ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance, and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Tz induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. As these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

2021-09-09 | PXD024276 | Pride

Site-specific glycan analysis of ErbB2 in breast cancer cell SKBR-3

2024-05-24 | PXD039837 | Pride

Site-specific glycan analysis of epidermal growth factor receptor (EGFR)

Project description:This study provides site-specific profiles of asparagine-linked and serine/threonine-linked glycosylations on ErbB2, a therapeutic target RTK for ErbB2-positive cancer, through structural analysis of recombinant ErbB2 extracellular region and endogenous ErbB2 from ErbB2-positive breast cancer cells. Furthermore, comparison of the N-glycosylated structures of the extracellular regions of ErbB2 and its homologue, the epidermal growth factor receptor (EGFR), showed differences in the distribution and density of N-glycans on both molecules, providing new insights into the different activation mechanisms of ErbB2 and EGFR from a glycan perspective.

2024-05-24 | PXD039836 | Pride

Site-specific glycan analysis of epidermal growth factor receptor 2

2024-05-21 | PXD039834 | Pride

Site-specific glycan analysis of CHO cell expressed epidermal growth factor receptor 2

2024-05-21 | PXD039835 | Pride

ErbB2 Site-Specific α2,6-Sialylation Regulates Gastric Cancer Cell Sensitivity to Trastuzumab

Project description:The clinical performance of trastuzumab in the treatment of ErbB2-positive gastric cancer is severely hampered by the emergence of molecular resistance. The glycosylation landscape of ErbB2’s extracellular domain, and the molecular mechanisms through which it tunes gastric cell malignancy, including the acquisition of trastuzumab resistance, remain elusive. We show that the expression of ErbB2 sialylated glycoforms holds clinical utility in the prediction of clinical outcome and stratification of gastric cancer patients. In-depth glycoproteomic and glycomic analysis of ErbB2 extracellular region disclosed a site-specific profile in gastric cancer cells. We further demonstrate that ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites within the trastuzumab binding domain. Moreover, the abrogation of ST6Gal1-mediated α2,6-sialylation reshapes ErbB2 glycome and sensitizes gastric cancer cells to trastuzumab-induced cytotoxicity through receptor membrane stabilization and a downregulation of ErbB2 activation. Overall, this data demonstrates that aberrant sialylation tunes the molecular resistance of ErbB2-driven gastric cancer cells to trastuzumab.

2021-05-11 | PXD017609 | Pride

FOXF1 promoter-putative enhancer chromatin looping

Project description:To determine if there is a physical interaction between the FOXF1 promoter and putative enhancer sequences ~250kb upstream of the promoter chromosome conformation capture-on-chip (4C) analysis was performed. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. 4C analysis using 16q24.1 specific 3x720K arrays demonstrated physical interaction between the FOXF1 promoter and distant putative regulatory sequences, about 250 kb upstream in human pulomonary microvascular endothelial cells; 2 biological replicates performed; this chromatin looping was not detected in lymphoblasts that do not express FOXF1 and hence serve as a negative control.

2012-07-10 | E-GEOD-39256 | biostudies-arrayexpress

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