ArticleCell communication and signaling : CCS2022
GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- TogoPhosTAC as a delivery-ready platform for targeted protein dephosphorylation.Nature communications · 2026Article
- Article
- PP2Acα Deficiency in Vascular Smooth Muscle Cells Accelerates Aortic Aneurysm and Dissection by Regulating KLF4 Phosphorylation and Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HBP-A Attenuates Knee Osteoarthritis Progression via MLK3/P38/HDAC4 Axis-Mediated Dual Protection of Articular Cartilage and Quadriceps.Journal of cellular and molecular medicine · 2025Article
- Special Issue: MAPK Signaling Cascades in Human Health and Diseases.International journal of molecular sciences · 2024Article
- Microcystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells.Toxicon : official journal of the International Society on Toxinology · 2024Article
- Phosphorylation of PP2Ac by PKC is a key regulatory step in the PP2A-switch-dependent AKT dephosphorylation that leads to apoptosis.Cell communication and signaling : CCS · 2024Article
- Genetic variation in patent foramen ovale: a case-control genome-wide association study.Frontiers in genetics · 2024Article
- PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- Proteomics reveals the potential mechanism of Tanshinone IIA in promoting theRegenerative therapy · 2022Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundG protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH.
methodsHere we used kinase activity assays of PI3K and followed phosphorylation state of proteins using specific antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein-protein interactions. Apoptosis was detected by TUNEL assay and PARP1 cleavage.
resultsWe identified the mechanism that allows the unique stimulated inactivation of AKT and show that the main regulator of this process is the phosphatase PP2A, operating with the non-canonical regulatory subunit IGBP1. In resting cells, an IGBP1-PP2Ac dimer binds to PI3K, dephosphorylates the inhibitory pSer608-p85 of PI3K and thus maintains its high basal activity. Upon GqPCR activation, the PP2Ac-IGBP1 dimer detaches from PI3K and thus allows the inhibitory dephosphorylation. At this stage, the free PP2Ac together with IGBP1 and PP2Aa binds to AKT, causing its dephosphorylation and inactivation.
conclusionOur results show a stimulated shift of PP2Ac from PI3K to AKT termed "PP2A switch" that represses the PI3K/AKT pathway, providing a unique mechanism of GPCR-stimulated dephosphorylation. Video Abstract.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.