title: Effect of diadenosine polyphosphates in achondroplasic chondrocytes: inhibitory effect of Ap4A on FGF9 induced MAPK cascade.
abstract: Achondroplasia is characterised by a mutation in the gene that encodes for the FGF receptor type 3 (FGFR3), producing a hyperactivation of this receptor and a subsequent increase in MAPK activity. We have tested the ability of nucleotides to decrease the activation of MAPK in chondrocytes with achondroplasic FGFR3 receptor. Diadenosine tetraphosphate, Ap(4)A, reduced the phosphorylation of pERK1/2 triggered by FGF9 (38% reduction). Ap(4)A diminished the expression of achondroplasic FGFR3 receptor (65% reduction), stimulating FGFR3 receptor degradation. The action of Ap(4)A seems to be mediated by a dinucleotide receptor rather than by any other ATP receptor.
authors.affiliation: Departamento de Bioquímica y Biología Molecular IV, E.U. Optica, Universidad Complutense de Madrid, c/Arcos de Jalón s/n, 28037 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Guzmán-Aránguez
authors.forename: Marta
authors.initials: M
authors.lastname: Irazu
authors.forename: Avner
authors.initials: A
authors.lastname: Yayon
authors.forename: Jesús
authors.initials: J
authors.lastname: Pintor
mesh_terms: D000130:Achondroplasia / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D051525:Fibroblast Growth Factor 9 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020935:MAP Kinase Signaling System; D051381:Rats; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism
chemical_list: D015226:Dinucleoside Phosphates; C496461:Fgf9 protein, rat; D051525:Fibroblast Growth Factor 9; C069820:Fgfr3 protein, rat; C020733:diadenosine tetraphosphate; D051498:Receptor, Fibroblast Growth Factor, Type 3