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PXD003660-1

PXD003660 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEarly Signaling Dynamics of EGFR
DescriptionDespite 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.
HostingRepositoryPRIDE
AnnounceDate2016-06-24
AnnouncementXMLSubmission_2016-06-24_06:52:02.xml
DigitalObjectIdentifierhttp://dx.doi.org/10.6019/PXD003660
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRaven Reddy
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; phosphorylated residue; iodoacetamide derivatized residue; TMT6plex-126 reporter+balance reagent acylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-02-18 12:12:13ID requested
12016-06-24 06:52:03announced
Publication List
Reddy RJ, Gajadhar AS, Swenson EJ, Rothenberg DA, Curran TG, White FM, Early signaling dynamics of the epidermal growth factor receptor. Proc Natl Acad Sci U S A, 113(11):3114-9(2016) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: EGFR
Mass spectrometry
tyrosine phosphorylation
systems biology
Contact List
Forest White
contact affiliationMassachusetts Institute of Technology
contact emailfwhite@mit.edu
lab head
Raven Reddy
contact affiliationMassachusetts Institute of Technology
contact emailravenr@mit.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
Repository Record List
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