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PXD023893

PXD023893 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSmoothened Transduces Hedgehog Signals via Activity-Dependent Sequestration of PKA Catalytic Subunits
DescriptionThe Hedgehog (Hh) pathway is essential for organ development, homeostasis, and regeneration. Dysfunction of this cascade drives several cancers. To control expression of pathway target genes, the G protein-coupled receptor (GPCR) Smoothened (SMO) activates glioma-associated (GLI) transcription factors via an unknown mechanism. Here we show that, rather than conforming to traditional GPCR signaling paradigms, SMO activates GLI by binding and sequestering protein kinase A (PKA) catalytic subunits at the membrane. This sequestration, triggered by GPCR kinase (GRK)-mediated phosphorylation of SMO intracellular domains, prevents PKA from phosphorylating soluble substrates, releasing GLI from PKA-mediated inhibition. Our work provides a mechanism directly linking Hh signal transduction at the membrane to GLI transcription in the nucleus. This process is more fundamentally similar between species than prevailing hypotheses suggest. The mechanism described here may apply broadly to other GPCR- and PKA-containing cascades in diverse areas of biology.
HostingRepositoryPanoramaPublic
AnnounceDate2021-03-10
AnnouncementXMLSubmission_2021-03-10_12:18:59.391.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRuth Huttenhain
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListPhospho; Carbamidomethyl; Oxidation
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-01-29 16:14:51ID requested
12021-03-10 12:18:59announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: PRM, Phosphorylation, Smoothened
Contact List
Ruth Huttenhain
contact affiliationUCSF
contact emailruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliationUCSF
contact emailruth.huttenhain@ucsf.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI