ArticleThe Journal of biological chemistry2009
Differential inhibitor of Gbetagamma signaling to AKT and ERK derived from phosducin-like protein: effect on sphingosine 1-phosphate-induced endothelial cell migration and in vitro angiogenesis.
Article in The Journal of biological chemistry, 2009. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Pan-cancer signaling landscape linked to endothelial and immune Sphingosine-1-phosphate receptor 1 (S1PR1) expression.In silico pharmacology · 2026Article
- Article
- Akt Is Controlled by Bag5 through a Monoubiquitination to Polyubiquitination Switch.International journal of molecular sciences · 2023Article
- G Protein-Coupled receptors and heterotrimeric G proteins as cancer drivers.FEBS letters · 2020Review
- Protumoral bone marrow-derived cells migrate via Gβγ-dependent signaling pathways and exhibit a complex repertoire of RhoGEFs.Journal of cell communication and signaling · 2019Article
- cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits.The Journal of biological chemistry · 2019Article
- Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by GαThe Journal of biological chemistry · 2019Article
- Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor: EFFECT ON PKA LOCALIZATION AND P-Rex1 SIGNALING.The Journal of biological chemistry · 2016Article
- Key role of PI3Kγ in monocyte chemotactic protein-1-mediated amplification of PDGF-induced aortic smooth muscle cell migration.British journal of pharmacology · 2012Article
- Gβγ subunits inhibit Epac-induced melanoma cell migration.BMC cancer · 2011Article
- Dissociation of the G protein βγ from the Gq-PLCβ complex partially attenuates PIP2 hydrolysis.The Journal of biological chemistryArticle
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Differential inhibitors of Gbetagamma-effector regions are required to dissect the biological contribution of specific Gbetagamma-initiated signaling pathways. Here, we characterize PhLP-M1-G149, a Gbetagamma-interacting construct derived from phosducin-like protein 1 (PhLP) as a differential inhibitor of Gbetagamma, which, in endothelial cells, prevented sphingosine 1-phosphate-induced phosphorylation of AKT, glycogen synthase kinase 3beta, cell migration, and tubulogenesis, while having no effect on ERK phosphorylation or hepatocyte growth factor-dependent responses. This construct attenuated the recruitment of phosphoinositide 3-kinase gamma (PI3Kgamma) to the plasma membrane and the signaling to AKT in response to Gbetagamma overexpression. In coimmunoprecipitation experiments, PhLP-M1-G149 interfered with the interaction between PI3Kgamma and Gbetagamma. Other PhLP-derived constructs interacted with Gbetagamma but were not effective inhibitors of Gbetagamma signaling to AKT or ERK. Our results indicate that PhLP-M1-G149 is a suitable tool to differentially modulate the Gbetagamma-initiated pathway linking this heterodimer to AKT, endothelial cell migration, and in vitro angiogenesis. It can be also useful to further characterize the molecular determinants of the Gbetagamma-PI3Kgamma interaction.
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Registered trials
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.