The role of Grb7 adapters, Grb7, Grb10, and Grb14, was investigated in Xenopus oocytes expressing fibroblast growth factor receptors (FGFR). FGF-induced maturation of FGFR-expressing oocytes was blocked by previous injection of Grb7 or Grb14, but not Grb10. This effect correlated with Grb7/14 binding to the receptor, and inhibition of the Ras-dependent pathway. Interestingly, the phosphorylated insulin receptor interacting region (PIR) and Src 2 homology domains (SH2) of Grb7 and Grb14 were differently implicated in the inhibition of FGFR signalling. This study provided further evidence for specificity of the biological action of the Grb7 adapters on receptor tyrosine kinase signalling.
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http://dx.doi.org/10.1016/s0014-5793(03)00726-9 | DOI Listing |
J Xenobiot
January 2025
School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Chlorpyrifos (CPF) is a broad-spectrum organophosphate insecticide. Long-term exposure to low levels of CPF is associated with neurodevelopmental and neurodegenerative disorders. The mechanisms leading to these effects are still not fully understood.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. Electronic address:
SLC17A3 localized to the apical membrane of the renal proximal tubules has been implicated in the urinary excretion of drugs and endogenous/exogenous metabolites transported into the tubules by OAT1 and OAT3. Because SLC17A3 mediates the facilitated diffusion of organic anions, which requires a sensitive and rapid assay, no system has been established to evaluate its transport activity in mammalian cells. In this study, we demonstrated that the exposure of cells expressing click beetle luciferase (bLuc) and SLC17A3 to D-luciferin produces marked bioluminescence, which enables the evaluation of SLC17A3 function.
View Article and Find Full Text PDFBr J Pharmacol
January 2025
Department of Physiology and Pharmacology, School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Background And Purpose: The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ protein, likely through the inhibition of G-protein gated K (GIRK) channels. Here, we investigated the mechanism of ETX inhibition (block) of different GIRKs.
Experimental Approach: We studied ETX inhibition of GIRK channels expressed in Xenopus oocytes with or without their physiological activator, the G protein subunit dimer Gβγ.
Neurotoxicology
January 2025
Laboratoire Physiologie, Ecologie et Environnement (P2E), Université d'Orléans, UR 1207, USC-INRAE 1328, 1 rue de Chartres, Orléans 45067, France; Institut Universitaire de France (IUF), 1 rue Descartes, Paris 75005, France. Electronic address:
Although neonicotinoids were considered safe for mammals for many decades, recent research has proven that these insecticides can alter cholinergic functions by interacting with neuronal nicotinic acetylcholine (ACh) receptors (nAChRs). One such receptor is the heteromeric α4β2 nAChR, which exists under two different stoichiometries: high sensitivity and low sensitivity α4β2 nAChRs. To replace these insecticides, new classes of insecticides have been developed, such as, sulfoximine, sulfoxaflor, and the butenolide, flupyradifurone.
View Article and Find Full Text PDFJ Biol Chem
January 2025
School of Biological Sciences, University of Utah, Salt Lake City, Utah, USA; Department of Psychiatry, University of Utah, Salt Lake City, Utah, USA; George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. In mammals, there are 16 individual nAChR subunits allowing for numerous possible heteromeric compositions. nAChRs assembled from α7 or α9 subunits will form as homopentamers.
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