This study investigates the role of Rho GTPases, specifically Cdc42, Rac1, and RhoA, in platelet-derived growth factor receptors (PDGFRα and PDGFRβ) signaling. Signal transducer and activator of transcription (STAT) proteins, essential for cellular processes such as proliferation and immune response, are activated downstream of PDGFRs. Dysregulation of these pathways is linked to various diseases, including cancer. The current study examines the effects of Rho GTPase depletion on PDGFR phosphorylation, STAT protein stability, and downstream signaling. Results indicate that depletion of Cdc42, Rac1, or RhoA impairs PDGFR phosphorylation and reduces STAT1 and STAT3 signaling, without significantly affecting AKT and ERK1/2 pathways. The findings highlight the critical regulatory roles of Rho GTPases in PDGFR-mediated STAT signaling.
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http://dx.doi.org/10.1016/j.bbrep.2024.101828 | DOI Listing |
Alzheimers Dement
December 2024
University of Western Ontario, London, ON, Canada.
Background: Previously, we identified macropinocytosis as a novel mechanism for direct and rapid trafficking of cell surface APP to lysosomes, bypassing early and late endosomes. This process depends on the activity of Arf6 and several Rho-GTPases, and inhibition of macropinocytosis reduces amyloid-beta (Aβ) production. Macropinocytosis is relatively unstudied in neurons and neuronal cells.
View Article and Find Full Text PDFNat Commun
January 2025
Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, P. R. China.
Delivering plasmid DNA (pDNA) to solid tumors remains a significant challenge due to the requirement for multiple transport steps and the need to promote delivery efficiency. Herein, we present a virus-mimicking hybrid lipoplex, composed of an arginine-rich cationic lipid, hyaluronic acid derivatives coated gold nanoparticles, and pDNA. This system induces cytoskeletal rearrangements through "outside-in" mechanical and "inside-out" biochemical signaling, overcoming intra- and intercellular barriers to enhance pDNA delivery.
View Article and Find Full Text PDFJ Cell Sci
January 2025
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Ligand binding to EGFR activates Rho family GTPases, triggering actin cytoskeleton reorganization, cell migration and invasion. Activated EGFR is also rapidly endocytosed but the role of EGFR endocytosis in cell motility is poorly understood. Hence, we used live-cell microscopy imaging to demonstrate that endogenous fluorescently labeled VAV2, a guanine nucleotide exchange factor for Rho GTPases, is co-endocytosed with EGFR in genome-edited human oral squamous cell carcinoma (HSC3) cells, an in vitro model for head-and-neck cancer where VAV2 is known to promote metastasis and associates with poor prognosis.
View Article and Find Full Text PDFFront Pediatr
December 2024
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States.
RHOBTB2 is a member of the Rho GTPases subfamily of signaling proteins, known tumor suppressors whose loss of function and decreased expression is associated with cancer onset. Beyond its cancer-related role, RHOBTB2 is implicated in rare neurodevelopmental disorders, specifically -related disorders, recognized in 2018 as a subtype of developmental and epileptic encephalopathies (DEE). Common symptoms of these disorders include early-onset epilepsy, severe intellectual disability, microcephaly, and movement disorders.
View Article and Find Full Text PDFFASEB J
December 2024
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine Jilin University, Center of Infectious Diseases and Pathogen Biology, Department of Infectious Diseases, First Hospital of Jilin University, Changchun, China.
Salmonella enterica serovar Typhimurium (S. Typhimurium) poses a serious threat to human and animal health, and there is an urgent need to develop new therapeutic agents. In our in vivo study, ginsenoside Ro (Ro) reduced the mortality rate of S.
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