{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garcia-Marcos M"],"funding":["National Institute of Neurological Disorders and Stroke","National Institute of General Medical Sciences"],"pagination":["e65620"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8034979"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10"],"pubmed_abstract":["It has become evident that activation of heterotrimeric G-proteins by cytoplasmic proteins that are not G-protein-coupled receptors (GPCRs) plays a role in physiology and disease. Despite sharing the same biochemical guanine nucleotide exchange factor (GEF) activity as GPCRs in vitro, the mechanisms by which these cytoplasmic proteins trigger G-protein-dependent signaling in cells have not been elucidated. Heterotrimeric G-proteins can give rise to two active signaling species, Gα-GTP and dissociated Gβγ, with different downstream effectors, but how non-receptor GEFs affect the levels of these two species in cells is not known. Here, a systematic comparison of GPCRs and three unrelated non-receptor proteins with GEF activity in vitro (GIV/Girdin, AGS1/Dexras1, and Ric-8A) revealed high divergence in their contribution to generating Gα-GTP and free Gβγ in cells directly measured with live-cell biosensors. These findings demonstrate fundamental differences in how receptor and non-receptor G-protein activators promote signaling in cells despite sharing similar biochemical activities in vitro."],"journal":["eLife"],"pubmed_title":["Complementary biosensors reveal different G-protein signaling modes triggered by GPCRs and non-receptor activators."],"pmcid":["PMC8034979"],"funding_grant_id":["R01NS117101","R01GM136132"],"pubmed_authors":["Garcia-Marcos M"],"additional_accession":[]},"is_claimable":false,"name":"Complementary biosensors reveal different G-protein signaling modes triggered by GPCRs and non-receptor activators.","description":"It has become evident that activation of heterotrimeric G-proteins by cytoplasmic proteins that are not G-protein-coupled receptors (GPCRs) plays a role in physiology and disease. Despite sharing the same biochemical guanine nucleotide exchange factor (GEF) activity as GPCRs in vitro, the mechanisms by which these cytoplasmic proteins trigger G-protein-dependent signaling in cells have not been elucidated. Heterotrimeric G-proteins can give rise to two active signaling species, Gα-GTP and dissociated Gβγ, with different downstream effectors, but how non-receptor GEFs affect the levels of these two species in cells is not known. Here, a systematic comparison of GPCRs and three unrelated non-receptor proteins with GEF activity in vitro (GIV/Girdin, AGS1/Dexras1, and Ric-8A) revealed high divergence in their contribution to generating Gα-GTP and free Gβγ in cells directly measured with live-cell biosensors. These findings demonstrate fundamental differences in how receptor and non-receptor G-protein activators promote signaling in cells despite sharing similar biochemical activities in vitro.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2024-02-15T15:50:50.581Z","creation":"2022-02-09T15:47:39.985Z"},"accession":"S-EPMC8034979","cross_references":{"pubmed":["33787494"],"doi":["10.7554/eLife.65620"]}}