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Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human HeLa cells and MCF10A cells subject to EGF stimulation

ABSTRACT: This SuperSeries is composed of the following subset Series:; GSE6783: Expression data from HELA cells subject to EGF stimulation; GSE6784: Expression data from MCF10A cells subject to EGF stimulation Experiment Overall Design: Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Tal Shay

PROVIDER: E-GEOD-6786 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A module of negative feedback regulators defines growth factor signaling.

Amit Ido I Citri Ami A Shay Tal T Lu Yiling Y Katz Menachem M Zhang Fan F Tarcic Gabi G Siwak Doris D Lahad John J Jacob-Hirsch Jasmine J Amariglio Ninette N Vaisman Nora N Segal Eran E Rechavi Gideon G Alon Uri U Mills Gordon B GB Domany Eytan E Yarden Yosef Y

Nature genetics 20070225 4

Signaling pathways invoke interplays between forward signaling and feedback to drive robust cellular response. In this study, we address the dynamics of growth factor signaling through profiling of protein phosphorylation and gene expression, demonstrating the presence of a kinetically defined cluster of delayed early genes that function to attenuate the early events of growth factor signaling. Using epidermal growth factor receptor signaling as the major model system and concentrating on regula ...[more]

PMID: 17322878

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Transcription profiling of human HeLa cells stimulated with epidermal growth factor vs. unstimulated sampled at multiple time points to investigate the temporal regulation of the cellular EGFR cascade

Project description:HELA cells derived from human cervical tumor were subjected to EGF stimulation for 0,20,40,60,120,240 and 480 minutes. We used microarrays to understand the temporal regulation of the cellular EGFR cascade. Experiment Overall Design: HELA cells were grown in DMEM supplemented with 10% FCS and antibiotics. Cells were serum deprived for 24 hours. Following stimulation with 10 ng/ml EGF for 0,20,40,60,120,240 and 480 minutes.

2007-11-02 | E-GEOD-6783 | biostudies-arrayexpress

Transcription profiling of human MCF10A mammary gland epithelial cells stimulated with epidermal growth factor vs unstimulated and sampled at multiple time points to investidage the temporal regulation of the cellular EGFR cascade

Project description:MCF10A cells derived from spontaneously immortalized normal human mammary epithelia were subjected to EGF/SERUM stimulation for 0,20,40,60,120,240 and 480 minutes. We used microarrays to understand the temporal regulation of the cellular EGFR cascade. Experiment Overall Design: MCF10A cells were grown in DME:F12 medium supplemented with antibiotics, [10 mg/ml insulin, 0.1 mg/ml cholera toxin, 0.5 mg/ml hydrocortisone, heat-inactivated horse serum (5%); defined as 'serum' in the text] and 10ng/ml EGF. Cells were serum deprived for 24 hours. Following stimulation with EGF/SERUM for 0,20,40,60,120,240 and 480 minutes.

2007-11-01 | E-GEOD-6784 | biostudies-arrayexpress

Murine corticotroph pituitary AtT-20 cells: Crh treatment time course

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Early Signaling Dynamics of EGFR

Project description:Despite extensive study of the epidermal growth factor receptor (EGFR) signaling network, the immediate post-translational changes that occur in response to growth factor stimulation remain poorly characterized; as a result, the biological mechanisms underlying signaling initiation remain obscured. To address this deficiency, we have used a mass spectrometry-based approach to measure system-wide phosphorylation changes throughout the network with 10 second resolution in the 80 seconds after stimulation in response to a range of 8 growth factor concentrations. Significant changes were observed on proteins far downstream in the network as early as 10 seconds after stimulation, indicating a system capable of transmitting information quickly. Meanwhile, canonical members of the EGFR signaling network fall into clusters with distinct activation patterns. Shc and PI3K phosphorylation levels increase rapidly, but equilibrate within 20 s, while proteins like Gab1 and SHP2 show slower, sustained increases. Proximity ligation assays reveal that Shc and Gab1 phosphorylation patterns are representative of separate timescales for physical association with the receptor. Inhibition of phosphatases with vanadate reveals site-specific regulatory mechanisms, and also uncovers primed activating components in the network, including Src family kinases, whose inhibition impacts only a subset of proteins within the network. The results presented highlight the complexity of signaling initiation, and provide a window into exploring mechanistic hypotheses about RTK biology.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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EGF-dependent ubiquitinome, phosphorylation and interactome analysis in control and CYLD-deficient cells

Project description:Cylindromatosis tumor suppressor protein (CYLD) is deubiquitinase, best known as an essential negative regulator of the NFkB pathway. Previous studies have suggested an involvement of CYLD in epidermal growth factor (EGF)-dependent signal transduction as well, as it was found enriched within the tyrosine-phosphorylated complexes in cells stimulated with the growth factor. EGF receptor (EGFR) signaling participates in central cellular processes and its tight regulation, partly through ubiquitination cascades, is decisive for a balanced cellular homeostasis. Here, using a combination of mass spectrometry-based quantitative proteomic approaches with biochemical and immunofluorescence strategies, we demonstrate the involvement of CYLD in the regulation of the ubiquitination events triggered by EGF. Our data show that CYLD regulates the magnitude of ubiquitination of several major effectors of the EGFR pathway by assisting the recruitment of the ubiquitin ligase Cbl-b to the activated EGFR complex. Notably, the deficiency of CYLD impairs the interaction of EGFR with Cbl-b, which leads to a reduced ubiquitination of the receptor followed by its decreased degradation. This represents a previously uncharacterized strategy exerted by this deubiquitinase and tumors pressor for the negative regulation of a tumorigenic signaling pathway.

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Transcription profiling of human keratinocytes treated with TGFalpha and insulin

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