ArticleThe Journal of biological chemistry2012
Activation of p115-RhoGEF requires direct association of Gα13 and the Dbl homology domain.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- RhoA/Rho-Kinase Signaling in Vascular Smooth Muscle and Endothelium: Mechanistic Insights and Translational Implications in Hypertension.Biomolecules · 2025Review
- Hippo signaling pathway in cervical cancer: insights into mechanisms and therapeutic potential.Frontiers in oncology · 2025Review
- Patterning of the cell cortex by Rho GTPases.Nature reviews. Molecular cell biology · 2024Review
- GPCRs thatSmall GTPases · 2022Review
- GαJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.Pharmacology & therapeutics · 2021Review
- Emerging regulators of vascular smooth muscle cell migration.Journal of muscle research and cell motility · 2019Review
- Loss of ARHGEF1 causes a human primary antibody deficiency.The Journal of clinical investigation · 2019Article
- miRNA-30d serves a critical function in colorectal cancer initiation, progression and invasion via directly targeting the GNA13 gene.Experimental and therapeutic medicine · 2019Article
- ROS-dependent activation of RhoA/Rho-kinase in pulmonary artery: Role of Src-family kinases and ARHGEF1.Free radical biology & medicine · 2017Article
- p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation.The Journal of biological chemistry · 2017Article
- Potentiation of receptor responses induced by prolonged binding of GαFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- High expression of GNA13 is associated with poor prognosis in hepatocellular carcinoma.Scientific reports · 2016Article
- A Gα12-specific Binding Domain in AKAP-Lbc and p114RhoGEF.Journal of molecular signaling · 2016Article
- Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis.Nature cell biology · 2016Article
- Cytokinetic effects of Wee1 disruption in pancreatic cancer.Cell cycle (Georgetown, Tex.) · 2016Article
- The interaction of Gα13 with integrin β1 mediates cell migration by dynamic regulation of RhoA.Molecular biology of the cell · 2015Article
- Article
- Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells.The Journal of biological chemistry · 2015Article
- MicroRNA-31 controls G protein alpha-13 (GNA13) expression and cell invasion in breast cancer cells.Molecular cancer · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G(12) class of heterotrimeric G proteins and the monomeric GTPases. In addition to the canonical Dbl homology (DH) and pleckstrin homology domains that carry out the guanine nucleotide exchange factor (GEF) activity toward RhoA, these RhoGEFs also possess RGS homology (RH) domains that interact with activated α subunits of G(12) and G(13). Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by Gα(13), the exact mechanism of the stimulation has remained unclear. Using combined studies with small angle x-ray scattering, biochemistry, and mutagenesis, we identify an additional binding site for activated Gα(13) in the DH domain of p115. Small angle x-ray scattering reveals that the helical domain of Gα(13) docks onto the DH domain, opposite to the surface of DH that binds RhoA. Mutation of a single tryptophan residue in the α3b helix of DH reduces binding to activated Gα(13) and ablates the stimulation of p115 by Gα(13). Complementary mutations at the predicted DH-binding site in the αB-αC loop of the helical domain of Gα(13) also affect stimulation of p115 by Gα(13). Although the GAP activity of p115 is not required for stimulation by Gα(13), two hydrophobic motifs in RH outside of the consensus RGS box are critical for this process. Therefore, the binding of Gα(13) to the RH domain facilitates direct association of Gα(13) to the DH domain to regulate its exchange activity. This study provides new insight into the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G protein signaling.
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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.