PXD002460

PXD002460 is an original dataset announced via ProteomeXchange.

Title	Context-dependent regulatory mechanisms control site-specific information processing within the MEK/ERK module
Description	The impact of the cellular context and receptor type on the dynamics of phosphorylation cycles in signaling pathways are unclear. We employ an unbiased approach to identify network alterations that explain phosphorylation dynamics of the MEK/ERK module in response to hepatocyte growth factor or interleukin-6, comparing primary hepatocytes with the immortalized cell line HaCaT. By combining quantitative mass spectrometry with dynamic modeling, we elucidate the network structure in primary hepatocytes. For HaCaT, our model predicts additional dual feedback regulation, which we experimentally identify as DUSP6 and paxillin. Model analyses reveal switch-like ERK phospho-form distribution profiles in primary hepatocytes that are severely altered in HaCaT, explaining threshold, sensitivity and saturation behavior. We apply our approach to human hepatocellular carcinoma samples and identify, as predicted, elevated threonine-phosphorylated ERK levels in the tumor. This suggests that the prevalence of the mono-phosphorylated ERK rather than the doubly phosphorylated ERK is indicative for dysregulated proliferation.
HostingRepository	PRIDE
AnnounceDate	2016-02-08
AnnouncementXML	Submission_2016-02-08_00:52:20.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sajib Chakraborty
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-01 02:26:49	ID requested
⏵ 1	2016-02-08 00:52:21	announced

Iwamoto N, D'Alessandro LA, Depner S, Hahn B, Kramer BA, Lucarelli P, Vlasov A, Stepath M, B, ö, hm ME, Deharde D, Damm G, Seehofer D, Lehmann WD, Klingm, ü, ller U, Schilling M, Context-specific flow through the MEK/ERK module produces cell- and ligand-specific patterns of ERK single and double phosphorylation. Sci Signal, 9(413):ra13(2016) [pubmed]

curator keyword: Biological

submitter keyword: Phosphorylation, Systems biology, Mass spectrometry, Signal transduction, Cellular information processing

Marcel Schilling
contact affiliation	German Cancer Research Center (DKFZ) Systems Biology of Signal Transduction Im Neuenheimer Feld 280 69120 Heidelberg Germany
contact email	m.schilling@dkfz.de
lab head
Sajib Chakraborty
contact affiliation	DKFZ Heidelberg
contact email	s.chakraborty@dkfz.de
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/2016/02/PXD002460

PRIDE project URI

• PRIDE
  1. PXD002460
     1. Label: PRIDE project
     2. Name: Context-dependent regulatory mechanisms control site-specific information processing within the MEK/ERK module