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PXD011033

PXD011033 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHEK293 femtomolar GPCR signaling
DescriptionG protein-coupled receptors (GPCRs) are the largest class of cell surface signaling proteins; they participate in all physiological processes and are the targets of 30% of marketed drugs. Typically, nanomolar-micromolar concentrations of ligand are used to activate GPCRs in experimental systems. However, by measuring cAMP with increased spatial and temporal resolution, we can now detect GPCR responses to an extraordinarily wide range of ligand concentrations: from attomolar to millimolar. Mathematical modeling shows that the addition of femtomolar concentrations of ligand can activate a significant proportion of cells provided that a cell can be activated by 1-2 binding events. In addition to cAMP, activation of the endogenous b2-adrenoceptor (b2AR) and muscarinic M3R by femtomolar concentrations of ligand in cell lines and human cardiac fibroblasts causes sustained increases in nuclear ERK or cytosolic PKC, respectively. These responses are spatially and temporally distinct from those that occur at higher concentrations of ligand, and result in a unique proteomic profile. This highly sensitive signaling is dependent on the GPCRs forming pre-assembled higher-order signaling complexes at the plasma membrane. Recognizing that GPCRs respond to ultra-low concentrations of neurotransmitters and hormones challenges established paradigms of drug action and provides a new dimension of GPCR activation that is quite distinct from that typically observed.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:48:55.259.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSrgjan Chivchiristov
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList2x(13)C,4x(2)H labeled dimethylated L-lysine; alkylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-09-07 06:39:50ID requested
12018-10-11 09:24:05announced
22018-10-15 02:55:59announcedUpdated publication reference for PubMed record(s): 30301787.
32024-10-22 04:49:00announced2024-10-22: Updated project metadata.
Publication List
10.1126/scisignal.aan1188;
Civciristov S, Ellisdon AM, Suderman R, Pon CK, Evans BA, Kleifeld O, Charlton SJ, Hlavacek WS, Canals M, Halls ML, Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations. Sci Signal, 11(551):(2018) [pubmed]
Keyword List
submitter keyword: compartmentalized signaling,femtomolar, cAMP, b2AR, M3R, signaling complex, GPCR, highly sensitive, ultra-low
Contact List
Michelle Louise Halls
contact affiliationDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
contact emailmichelle.halls@monash.edu
lab head
Srgjan Chivchiristov
contact affiliationMonash University, Melbourne
contact emailsrgjan.chivchiristov@monash.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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