Les signaux des FGF : un mécanisme qui commence à être déchiffré

Abstract

Les FGF (fibroblast growth factors) sont des peptides multifonctionnels. Ils appartiennent à une famille qui compte actuellement neuf membres. Leur système de signalisation commence à être déchiffré ; il implique principalement trois catégories de composés moléculaires : une pléiade d’isoformes de récepteurs à activité tyrosine kinase et des corécepteurs qui sont des protéoglycanes à sulfate d’héparane; de nombreux effecteurs et seconds messagers impliqués dans la signalisation des facteurs de croissance et des neurotrophines ; des cibles nucléaires capables d’être directement activées par des FGF endogènes et des FGF exogènes internalisés.

Fibroblast growth factors (FGF) are encoded by at least nine distinct genes. They share a broad spectrum of biological functions and appear to be involved in various physiopathological processes including tumor development, atherogenesis, neurodegenerative diseases, neovascularization and genetic disorders. Signalling by FGF is mainly mediated through binding to both high-affinity tyrosine kinase receptors and low-affinity heparan sulfate proteoglycans associated with plasma membrane and extracellular matrix. Matrix proteoglycans appear to act as a storage depot or sink for FGF, whereas membrane proteogly cans function as co-receptors and facilitate signalling by the high-affinity receptors. Four genes encoding tyrosine kinase receptors have been identified, but alternative splicing produces multiple isoforms, some of which are putative secreted receptors. Signal transduction of tyrosine kinase receptors involves dimerization and autophosphorylation which mediate the activation of a myriad of signalling proteins and second-messengers, leading to changes in gene expression. However, there is mounting evidence to suggest that these receptors may not be sufficient for all aspects of FGF signalling. The fact that the nuclear localization of FGF1, FGF2 and FGF3 is found to be regulated in parallel with mitogenesis and differentiation, indeed, supports also a potential role for FGF in the direct regulation of transcription, replication or other nuclear events.