PXD003660-1

PXD003660 is an original dataset announced via ProteomeXchange.

Title	Early Signaling Dynamics of EGFR
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.
HostingRepository	PRIDE
AnnounceDate	2016-06-24
AnnouncementXML	Submission_2016-06-24_06:52:02.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD003660
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Raven Reddy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; phosphorylated residue; iodoacetamide derivatized residue; TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-02-18 12:12:13	ID requested
⏵ 1	2016-06-24 06:52:03	announced

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]

curator keyword: Biological

submitter keyword: EGFR

Mass spectrometry

tyrosine phosphorylation

systems biology

Forest White
contact affiliation	Massachusetts Institute of Technology
contact email	fwhite@mit.edu
lab head
Raven Reddy
contact affiliation	Massachusetts Institute of Technology
contact email	ravenr@mit.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/06/PXD003660

PRIDE project URI

• PRIDE
  1. PXD003660
     1. Label: PRIDE project
     2. Name: Early Signaling Dynamics of EGFR