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PXD069348

PXD069348 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAdenovirus E4ORF1 activates isoform-specific phosphatidylinositol 3-kinase signaling
DescriptionThe human adenovirus serotype 5 E4ORF1 (Ad5E4ORF1) protein promotes primary endothelial cell survival and angiocrine functions by hijacking the cellular phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. However, the mechanism by which E4ORF1 activates PI3K in vascular cells remains largely unknown. Here we show that Ad5E4ORF1 recruits multiple host scaffold proteins including DLG1, which promotes AKT activation by both Ad5E4ORF1 and cell receptor agonists. Furthermore, Ad5E4ORF1 specifically engages human PI3K isoform p110a-p85b through multi-domain interactions exclusively with p110a. Importantly, various serotypes of E4ORF1 proteins differentially interact with p110a leading to graded AKT activation in endothelial cells. We propose that E4ORF1 specifically recognizes p110a-p85b and allosterically activates PI3K through multiple direct contacts with p110a, setting the stage of endothelial cell survival and homeostatic angiogenic functions.
HostingRepositoryPRIDE
AnnounceDate2026-01-05
AnnouncementXMLSubmission_2026-01-04_16:08:23.079.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTuKiet Lam
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-10-11 01:00:31ID requested
12026-01-04 16:08:24announced
Publication List
Geng F, Kobayashi M, Lin Y, Gomez-Salinero JM, Romano D, Kanyo J, Geng J, Liu Y, Ginsberg M, Shieh JH, Chen K, Lam TT, Rafii A, Rabbany SY, Lis R, Rafii S, Adenovirus E4ORF1 activates isoform-specific phosphatidylinositol 3-kinase signaling in human endothelial cells. J Biol Chem, 302(1):110947(2026) [pubmed]
10.1016/j.jbc.2025.110947;
Keyword List
submitter keyword: Adenovirus
AKT
angiogenesis
DLG1
E4ORF1
endothelium
phosphatidylinositol-3-kinase.
Contact List
TuKiet Lam
contact affiliationKeck MS & Proteomics Resource Yale School of Medicine
contact emailtukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliationYale University
contact emailtukiet.lam@yale.edu
dataset submitter
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Dataset FTP location
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