ArticleOncogene2013
PKCα phosphorylation of RhoGDI2 at Ser31 disrupts interactions with Rac1 and decreases GDI activity.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
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- Binding of the Andes Virus Nucleocapsid Protein to RhoGDI Induces the Release and Activation of the Permeability Factor RhoA.Journal of virology · 2021Article
- AKF-PD alleviates diabetic nephropathy via blocking the RAGE/AGEs/NOX and PKC/NOX Pathways.Scientific reports · 2019Article
- XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin-mediated Rho-GDIβ mRNA stability.International journal of cancer · 2018Article
- Assessment of roles for the Rho-specific guanine nucleotide dissociation inhibitor Ly-GDI in platelet function: a spatial systems approach.American journal of physiology. Cell physiology · 2017Article
- A mathematical model of GTPase pattern formation during single-cell wound repair.Interface focus · 2016Review
- Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016Review
- The MAP3K ZAK, a novel modulator of ERK-dependent migration, is upregulated in colorectal cancer.Oncogene · 2016Article
- Article
- Copper-catalyzed azide-alkyne cycloaddition (click chemistry)-based detection of global pathogen-host AMPylation on self-assembled human protein microarrays.Molecular & cellular proteomics : MCP · 2014Article
- Metastasis suppressors in breast cancers: mechanistic insights and clinical potential.Journal of molecular medicine (Berlin, Germany) · 2014Review
- The faces and friends of RhoGDI2.Cancer metastasis reviews · 2012Review
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Rho family GTPases control a diverse range of cellular processes, and their deregulation has been implicated in human cancer. Guanine nucleotide dissociation inhibitors (GDIs) bind and sequester GTPases in the cytosol, restricting their actions. RhoGDI2 is a member of the GDI family that acts as a metastasis suppressor in a variety of cancer types; however, very little is known about the regulation of this protein. Here, we present a mechanism for inactivation of RhoGDI2 via protein kinase C (PKC) phosphorylation of Ser31 in a region that contacts GTPases. In cells, RhoGDI2 becomes rapidly phosphorylated at Ser31 in response to phorbol 12-myristate 13-acetate stimulation. Based on the effects of pharmacological inhibitors and knockdown by siRNA, we determine that conventional type PKCα is responsible for this phosphorylation. Phospho-mimetic S31E-RhoGDI2 exhibits reduced binding to Rac1 relative to wild type, with a concomitant failure to reduce levels of activated endogenous Rac1 or remove Rac1 from membranes. These results reveal a mechanism of downregulation of RhoGDI2 activity through PKC-mediated phosphorylation of Ser31. We hypothesize that this mechanism may serve to neutralize RhoGDI2 function in tumors that express RhoGDI2 and active PKCα.
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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.