Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell signaling response to cytokines measured by high throughput microscopy

ABSTRACT: -

SUBMITTER: Mario Niepel

PROVIDER: LDS-1125 | LINCS | 2017-09-19

REPOSITORIES: LINCS

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	HMS_LINCS&file=LDS-1125.tar.gz	Other

Items per page:

1 - 1 of 1

Publications

Profiles of Basal and stimulated receptor signaling networks predict drug response in breast cancer lines.

Niepel Mario M Hafner Marc M Pace Emily A EA Chung Mirra M Chai Diana H DH Zhou Lili L Schoeberl Birgit B Sorger Peter K PK

Science signaling 20130924 294

Identifying factors responsible for variation in drug response is essential for the effective use of targeted therapeutics. We profiled signaling pathway activity in a collection of breast cancer cell lines before and after stimulation with physiologically relevant ligands, which revealed the variability in network activity among cells of known genotype and molecular subtype. Despite the receptor-based classification of breast cancer subtypes, we found that the abundance and activity of signalin ...[more]

PMID: 24065145

Similar Datasets

Cell signaling response to growth factors measured by high throughput microscopy

Project description:-

2015-09-23 | LDS-1124 | LINCS

Cell signaling response to growth factors measured by ELISA

Project description:-

2015-09-23 | LDS-1126 | LINCS

Activation of the ATR kinase by the RPA-binding protein ETAA1

Project description:The ATR kinase is a master regulator of cellular responses to DNA damage and replication stress that is activated by a complex mechanism involving its binding partner ATRIP, RPA-coated ssDNA, the 9-1-1 complex and TopBP1. Here, we discovered a new ATR activation mechanism in human cells, mediated by the uncharacterized protein ETAA1 (Ewing’s tumor-associated antigen 1). From a comprehensive proteomic survey of protein recruitment to DNA double-strand break-modified chromatin, we identified ETAA1 as a factor that accumulates at DNA damage sites via an RPA-binding motif, and which has an important role in promoting cell survival and preventing replication fork breakage after genotoxic insults. Mechanistically, we show that ETAA1 harbors a conserved domain that potently and directly stimulates ATR kinase activity independent of TopBP1 and 9-1-1, and which is essential for the function of ETAA1 in the DNA damage response. Consistently, ablation of ETAA1 shows profound synthetic lethality with TopBP1 knockdown, resulting from massive replication fork collapse and abrogation of ATR-dependent signaling. Finally, we show that ETAA1 levels in cancer cell lines inversely correlate with their dependency on TopBP1 for ATR activation, and that overexpression of ETAA1 partially restores ATR-dependent signaling after loss of TopBP1. Together, these findings establish a new mechanism of ATR activation in human cells that operates in parallel with, but independent of, the canonical TopBP1-mediated pathway.

2016-09-30 | PXD003529 | Pride

Modular bottom-up proteomic sample preparation for high-throughput applications

Project description:A collection of digital automated proteomic sample preparation protocols detail three optimized step-by-step methods to: (A) lyse Gram-negative bacteria and fungal cells; (B) quantify the amount of protein extracted; and (C) normalize the amount of protein and set up tryptic digestion. These protocols have been developed to facilitate rapid, low variance sample preparation of hundreds of samples, be easily implemented on widely-available Beckman-Coulter Biomek automated liquid handlers, and allow flexibility for future protocol development

2022-02-14 | PXD029122 | Pride

Proteomic profiling of human monocytes stimulated in vitro with N. meningitidis

Project description:Meningococcal sepsis is an overwhelming form of the sepsis syndrome which may cause mortality within 12-24 hours in previously healthy children and adults, where the causative infectious agent is N. meningitidis, an obligate human pathogen. The genomic changes induced by N. meningitidis are modulated by the anti-inflammatory cytokine interleukin-10 (IL-10), which is present in large quantities in plasma from patients with meningococcal sepsis. This present study investigated kinase activities in human monocytes stimulated by N. meningitidis and IL-10. The first aim was to identify array peptides that could indicate which signaling pathways were activated or inhibited by the host response to the meningococci. The second aim was to detect whether IL-10 affected N. meningitidis-nduced phosphorylation of array peptides, in order to identify potential targets of the IL-10 anti-inflammatory response. We approached this using a strategy where elutriation-purified human monocytes are stimulated in vitro with N. meningitidis and IL-10, with concentrations corresponding to previously measured levels in patients with fulminant meningococcal septicemia. This work examined activation or inhibition of signaling pathways mediated by tyrosine kinases when purified human monocytes are in vitro incubated with N. meningitidis in the presence or absence of IL-10.

2017-12-15 | E-MTAB-4795 | biostudies-arrayexpress

Kinase activity profiling of human locally advanced rectal cancer samples

Project description:Locally advanced rectal cancer characterized by multiplex kinase activity profiling

2010-08-05 | E-TABM-913 | biostudies-arrayexpress

Hypoxic tumor kinase signaling mediated by STAT5A in development of castration-resistant prostate cancer

Project description:To examine changes in tyrosine kinase activity in prostate cancer tumors developing resistance to androgen deprivation therapy and to compare these to changes in tyrosine kinase activity occuring in cell lines exposed to oxygen deficiency (hypoxia)

2013-04-15 | E-MTAB-1572 | biostudies-arrayexpress

Proteomic profiling by array of tyrosine kinase activity in metastatic malignant melanoma from human tissue specimens

Project description:Tyrosine kinase activity profiling of metatstatic malignant melanoma and normal skin tissue samples was performed using peptide kinase arrays. All samples were run in triplicates with and withouth inhbitor PLX4032 and Sutent Malate in order to identify how tyrosine kinases responds to kinase inhibitor treatment, ex vivo.

2013-01-17 | E-MTAB-1245 | biostudies-arrayexpress

A high throughput pipeline for antibody validation

Project description:Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we show that an inverted version of WB allows parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS). The pipeline provides means for large-scale implementation of concepts proposed by an international working group on antibody validation (IWGAV).

2018-07-26 | PXD010510 | Pride

Non-canonical EphA2 signaling is a driver of tumor-endothelial cell interactions and metastatic dissemination in BRAF inhibitor resistant melanoma

Project description:Acquired BRAF/MEK inhibitor resistance in melanoma results in a new transcriptional state associated with increased risk of metastasis. Here, we identified non-canonical EphA2 signaling as a driver of the resistance-associated metastatic state. We used mass spectrometry-based proteomic and phenotypic assays to demonstrate that the expression of active non-canonical EphA2-S897E in melanoma cells led to a mesenchymal-to-amoeboid transition (MAT) driven by Cdc42 activation. The induction of MAT promoted melanoma cell invasion, survival under shear stress, adhesion to endothelial cells under continuous flow conditions, increased permeability of endothelial cell monolayers and stimulated melanoma transendothelial cell migration. In vivo, melanoma cells expressing EphA2-S897E or active Cdc42 showed superior lung retention following tail-vain injection. Analysis of BRAF inhibitor-sensitive and -resistant melanoma cells demonstrated resistance to be associated with an MAT switch, upregulation of Cdc42 activity, increased invasion, and transendothelial migration. The drug resistant metastatic state was dependent upon histone deacetylase 8 (HDAC8) activity. Silencing of HDAC8 lead to inhibition of EphA2 and AKT phosphorylation, reduced invasion and impaired melanoma cell-endothelial cell interactions. In summary, we have demonstrated that the metastatic state associated with acquired BRAF inhibitor resistance is dependent on non-canonical EphA2 signaling, leading to increased melanoma-endothelial cell interactions and enhanced tumor dissemination.

2020-11-18 | PXD020250 | Pride