ArticlePloS one2012
Identification of a novel actin-binding domain within the Rho guanine nucleotide exchange factor TEM4.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 31 citations in OpenAlex.
- Biology, Physics, and Genetics of Intracranial Aneurysm Formation: A Review.Journal of neurological surgery. Part A, Central European neurosurgery · 2026Review
- Dynamic decoding of VEGF signaling and coordinated control of multiple phenotypes by the Src-TEM4-YAP pathway.Cell systems · 2025Article
- ARHGEF17/TEM4 regulates the cell cycle through control of G1 progression.The Journal of cell biology · 2025Article
- Case report: Expanding the phenotype ofFrontiers in neurology · 2022Article
- A commercial ARHGEF17/TEM4 antibody cross-reacts with Nuclear Mitotic Apparatus protein 1 (NuMA).PloS one · 2022Article
- TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia.Communications biology · 2021Article
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- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
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- Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms.Nature cell biology · 2020Article
- cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology-tribute to Karl H. Jakobs.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- Rho Guanine Nucleotide Exchange FactorCirculation. Genomic and precision medicine · 2018Article
- PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Flat cells come full sphere: Are mutant cytoskeletal-related proteins oncoprotein-monsters or useful immunogens?Human vaccines & immunotherapeutics · 2016Article
- Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates.Disease markers · 2016Review
- Phosphorylation of Cdc42 effector protein-4 (CEP4) by protein kinase C promotes motility of human breast cells.The Journal of biological chemistry · 2014Article
- RhoGEFs in cell motility: novel links between Rgnef and focal adhesion kinase.Current molecular medicine · 2014Review
- Rho GAPs and GEFs: controling switches in endothelial cell adhesion.Cell adhesion & migration · 2014Review
- TEM4 is a junctional Rho GEF required for cell-cell adhesion, monolayer integrity and barrier function.Journal of cell science · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Spatio-temporal activation of Rho GTPases is essential for their function in a variety of biological processes and is achieved in part by regulating the localization of their activators, the Rho guanine nucleotide exchange factors (RhoGEFs). In this study, we provide the first characterization of the full-length protein encoded by RhoGEF TEM4 and delineate its domain structure, catalytic activity, and subcellular localization. First, we determined that TEM4 can stimulate guanine nucleotide exchange on RhoA and the related RhoB and RhoC isoforms. Second, we determined that TEM4, like other Dbl RhoGEFs, contains a functional pleckstrin homology (PH) domain immediately C-terminal to the catalytic Dbl homology (DH) domain. Third, using immunofluorescence analysis, we showed that TEM4 localizes to the actin cytoskeleton through sequences in the N-terminus of TEM4 independently of the DH/PH domains. Using site-directed mutagenesis and deletion analysis, we identified a minimal region between residues 81 and 135 that binds directly to F-actin and has an ∼90-fold higher affinity for ATP-loaded F-actin. Finally, we demonstrated that a single point mutation (R130D) within full-length TEM4 abolishes actin binding and localization of TEM4 to the actin cytoskeleton, as well as dampens the in vivo activity of TEM4 towards RhoC. Taken together, our data demonstrate that TEM4 contains a novel actin binding domain and binding to actin is essential for TEM4 subcellular localization and activity. The unique subcellular localization of TEM4 suggests a spatially-restricted activity and expands the diversity of mechanisms by which RhoGEF function can be regulated.
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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.