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1: Biochem Pharmacol. 2007 Aug 1;74(3):448-56. Epub 2007 May 1.

Effect of diadenosine polyphosphates in achondroplasic chondrocytes: inhibitory
effect of Ap4A on FGF9 induced MAPK cascade.

Guzmán-Aránguez A, Irazu M, Yayon A, Pintor J.

Departamento de Bioquímica y Biología Molecular IV, E.U. Optica, Universidad
Complutense de Madrid, c/Arcos de Jalón s/n, 28037 Madrid, Spain.

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.

PMID: 17543287 [PubMed - indexed for MEDLINE]

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