ArticleThe Journal of biological chemistry2015
Epidermal growth factor activates the Rho GTPase-activating protein (GAP) Deleted in Liver Cancer 1 via focal adhesion kinase and protein phosphatase 2A.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Pp6-Pfkfb1 axis modulates intracellular bacterial proliferation by orchestrating host-pathogen metabolic crosstalk.PLoS pathogens · 2025Article
- Mechanosensitive biochemical imprinting of the talin interaction with DLC1 regulates RhoA activity and cardiomyocyte remodeling.Science advances · 2025Article
- ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/β-Catenin Signaling Pathway.Biochemical genetics · 2025Article
- Proteasomal turnover of the RhoGAP tumor suppressor DLC1 is regulated by HECTD1 and USP7.Scientific reports · 2022Article
- Cancer-Associated Point Mutations in theCancer research · 2020Article
- Targeting cell surface GRP78 enhances pancreatic cancer radiosensitivity through YAP/TAZ protein signaling.The Journal of biological chemistry · 2019Article
- fMLP-dependent activation of Akt and ERK1/2 through ROS/Rho A pathways is mediated through restricted activation of the FPRL1 (FPR2) receptor.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1.The Journal of cell biology · 2017Article
- Dual TORCs driven and B56 orchestrated signaling network guides eukaryotic cell migration.BMB reports · 2017Article
- Down-regulation of DLC1 in endothelial cells compromises the angiogenesis process.Cancer letters · 2017Article
- Calcineurin, the CaMolecular biology of the cell · 2017Article
- Curcumin inhibits growth of human breast cancer cells through demethylation of DLC1 promoter.Molecular and cellular biochemistry · 2017Article
- ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma.Oncotarget · 2016Article
- Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016Review
- DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer.Diagnostic pathology · 2016Article
- Tensin1 positively regulates RhoA activity through its interaction with DLC1.Biochimica et biophysica acta · 2015Article
- Chloride-hydrogen antiporters ClC-3 and ClC-5 drive osteoblast mineralization and regulate fine-structure bone patterning in vitro.Physiological reports · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deleted in Liver Cancer 1 (DLC1) is a RHO GTPase-activating protein (GAP) that negatively regulates RHO. Through its GAP activity, it modulates the actin cytoskeleton network and focal adhesion dynamics, ultimately leading to suppression of cell invasion and metastasis. Despite its presence in various structural and signaling components, little is known about how the activity of DLC1 is regulated at focal adhesions. Here we show that EGF stimulation activates the GAP activity of DLC1 through a concerted mechanism involving DLC1 phosphorylation by MEK/ERK and its subsequent dephosphorylation by protein phosphatase 2A (PP2A) and inhibition of focal adhesion kinase by MEK/ERK to allow the binding between DLC1 and PP2A. Phosphoproteomics and mutation studies revealed that threonine 301 and serine 308 on DLC1, known previously to be mutated in certain cancers, are required for DLC1-PP2A interaction and the subsequent activation of DLC1 upon their dephosphorylation. The intricate interplay of this "MEK/ERK-focal adhesion kinase-DLC1-PP2A" quartet provides a novel checkpoint in the spatiotemporal control of cell spreading and cell motility.
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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.