PXD002598

PXD002598 is an original dataset announced via ProteomeXchange.

Title	eNOS interactors in human cells
Description	Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of L-arginine and molecular oxygen into L-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist stimulated NO synthesis and decreased phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells.
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_10:13:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Froehlich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-24 03:43:18	ID requested
⏵ 1	2018-10-24 10:13:28	announced

Siragusa M, Fr, ö, hlich F, Park EJ, Schleicher M, Walther TC, Sessa WC, Stromal cell-derived factor 2 is critical for Hsp90-dependent eNOS activation. Sci Signal, 8(390):ra81(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: eNOS, Stromal cell-derived factor 2

Tobias Walther
contact affiliation	Professor of Genetics and Complex Diseases, Harvard University T.H. Chan School of Public Health Professor of Cell Biology, Harvard Medical School Associate Member, Broad Institute of MIT and Harvard
contact email	t.walther@hsph.harvard.edu
lab head
Florian Froehlich
contact affiliation	Harvard School of Public Health; Research Associate
contact email	froehlic@hsph.harvard.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/2018/10/PXD002598

PRIDE project URI

• PRIDE
  1. PXD002598
     1. Label: PRIDE project
     2. Name: eNOS interactors in human cells