PXD011033

PXD011033 is an original dataset announced via ProteomeXchange.

Title	HEK293 femtomolar GPCR signaling
Description	G 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:48:55.259.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Srgjan Chivchiristov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	2x(13)C,4x(2)H labeled dimethylated L-lysine; alkylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-07 06:39:50	ID requested
1	2018-10-11 09:24:05	announced
2	2018-10-15 02:55:59	announced	Updated publication reference for PubMed record(s): 30301787.
⏵ 3	2024-10-22 04:49:00	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: compartmentalized signaling,femtomolar, cAMP, b2AR, M3R, signaling complex, GPCR, highly sensitive, ultra-low

Michelle Louise Halls
contact affiliation	Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
contact email	michelle.halls@monash.edu
lab head
Srgjan Chivchiristov
contact affiliation	Monash University, Melbourne
contact email	srgjan.chivchiristov@monash.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/PXD011033

PRIDE project URI

• PRIDE
  1. PXD011033
     1. Label: PRIDE project
     2. Name: HEK293 femtomolar GPCR signaling