PXD002598 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-07-24 03:43:18 | ID requested | |
⏵ 1 | 2018-10-24 10:13:28 | announced | |
Publication List
Siragusa M, Fr, รถ, 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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: eNOS, Stromal cell-derived factor 2 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002598
- Label: PRIDE project
- Name: eNOS interactors in human cells