ArticlePloS one2017
The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- GPNMB-ECD drives acquired resistance to osimertinib in NSCLC via inducing tumor cell cytoskeletal reorganization.Cellular & molecular biology letters · 2026Article
- Regulation of H-type angiogenesis and permeability in the subchondral bone of osteoarthritis: the role of Slit3 and the Robo4/Rac1-GTP/ROS axis.Frontiers in cell and developmental biology · 2026Article
- Trastuzumab Decreases the Expression of G1/S Regulators and Syndecan-4 Proteoglycan in Human Rhabdomyosarcoma.International journal of molecular sciences · 2025Article
- Syndecan-4 interacts directly with β-parvin and regulates the ILK-PINCH-β-parvin complex, the β-parvin-β-PIX-Rac1 axis, and cardiomyocyte geometry in a sex-dependent manner.Frontiers in cell and developmental biology · 2025Article
- RhoGDI1 regulates cell-cell junctions in polarized epithelial cells.Frontiers in cell and developmental biology · 2024Article
- FtsZ phosphorylation pleiotropically affects Z-ladder formation, antibiotic production, and morphogenesis in Streptomyces coelicolor.Antonie van Leeuwenhoek · 2023Article
- Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.Biochemical pharmacology · 2022Review
- Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors.Cellular and molecular life sciences : CMLS · 2022Article
- Syndecan-4 in Tumor Cell Motility.Cancers · 2021Review
- Myoblast Migration and Directional Persistence Affected by Syndecan-4-Mediated Tiam-1 Expression and Distribution.International journal of molecular sciences · 2020Article
- Syndecan-4 Modulates Cell Polarity and Migration by Influencing Centrosome Positioning and Intracellular Calcium Distribution.Frontiers in cell and developmental biology · 2020Article
- Proteoglycans as Mediators of Cancer Tissue Mechanics.Frontiers in cell and developmental biology · 2020Review
- Heparan sulfate proteoglycan (HSPG) can take part in cell division: inside and outside.Cellular and molecular life sciences : CMLS · 2019Review
- Gene expression profiling identifies potential molecular markers of papillary thyroid carcinoma.Cancer biomarkers : section A of Disease markers · 2019Article
- Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition.FEBS letters · 2018Article
- Quantitative Proteome and Phosphoproteome Analyses ofMolecular & cellular proteomics : MCP · 2018Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.
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