ArticleThe Journal of biological chemistry2014
Functional cross-talk between ras and rho pathways: a Ras-specific GTPase-activating protein (p120RasGAP) competitively inhibits the RhoGAP activity of deleted in liver cancer (DLC) tumor suppressor by masking the catalytic arginine finger.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer metastasis.Cancer biology & therapy · 2017Trial
- From neural loss to regeneration: modulating cell death to enhance pluripotent stem cell graft survival and integration.Cell death & disease · 2026Review
- Clinically observed RASA1 missense mutants exhibit diverse RasGAP protein behaviors in vitro.The Journal of biological chemistry · 2026Article
- Clinically observedbioRxiv : the preprint server for biology · 2025Article
- Functional Classification and Interaction Selectivity Landscape of the Human SH3 Domain Superfamily.Cells · 2024Article
- A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling.Cells · 2023Review
- A Structural Network Analysis of Neuronal ArhGAP21/23 Interactors by Computational Modeling.ACS omega · 2023Article
- The potential therapeutic roles of Rho GTPases in substance dependence.Frontiers in molecular neuroscience · 2023Article
- Tandem engagement of phosphotyrosines by the dual SH2 domains of p120RasGAP.Structure (London, England : 1993) · 2022Article
- SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP.Nature communications · 2022Article
- Review
- Accessory proteins of the RAS-MAPK pathway: moving from the side line to the front line.Communications biology · 2021Review
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- Modeling the effect of prolonged ethanol exposure on global gene expression and chromatin accessibility in normal 3D colon organoids.PloS one · 2020Article
- SRC and ERK cooperatively phosphorylate DLC1 and attenuate its Rho-GAP and tumor suppressor functions.The Journal of cell biology · 2019Article
- Novel Tools towards Magnetic Guidance of Neurite Growth: (I) Guidance of Magnetic Nanoparticles into Neurite Extensions of Induced Human Neurons and In Vitro Functionalization with RAS Regulating Proteins.Journal of functional biomaterials · 2019Article
- RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability.Nature cell biology · 2019Article
- Controlling the Revolving and Rotating Motion Direction of Asymmetric Hexameric Nanomotor by Arginine Finger and Channel Chirality.ACS nano · 2019Review
- Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1.The Journal of cell biology · 2017Article
- Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins: A SYSTEMATIC APPROACH TOWARD SELECTIVE INACTIVATION OF RHO FAMILY PROTEINS.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The three deleted in liver cancer genes (DLC1-3) encode Rho-specific GTPase-activating proteins (RhoGAPs). Their expression is frequently silenced in a variety of cancers. The RhoGAP activity, which is required for full DLC-dependent tumor suppressor activity, can be inhibited by the Src homology 3 (SH3) domain of a Ras-specific GAP (p120RasGAP). Here, we comprehensively investigated the molecular mechanism underlying cross-talk between two distinct regulators of small GTP-binding proteins using structural and biochemical methods. We demonstrate that only the SH3 domain of p120 selectively inhibits the RhoGAP activity of all three DLC isoforms as compared with a large set of other representative SH3 or RhoGAP proteins. Structural and mutational analyses provide new insights into a putative interaction mode of the p120 SH3 domain with the DLC1 RhoGAP domain that is atypical and does not follow the classical PXXP-directed interaction. Hence, p120 associates with the DLC1 RhoGAP domain by targeting the catalytic arginine finger and thus by competitively and very potently inhibiting RhoGAP activity. The novel findings of this study shed light on the molecular mechanisms underlying the DLC inhibitory effects of p120 and suggest a functional cross-talk between Ras and Rho proteins at the level of regulatory proteins.
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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.