Abstracts
Résumé
Les RAMP (receptor activity-modifying protein) modifient le caractère fonctionnel des récepteurs couplés aux protéines G (RCPG) des peptides de la famille de la calcitonine. Il semble que l’on puisse étendre l’interaction des RAMP à d’autres RCPG de classe II, puisque ces protéines s’associent aux récepteurs de l’hormone parathyroïdienne, du glucagon et du VIP/PACAP (vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide) dénommé également R-VPAC1 (vasoactive-intestinal peptide PACAP receptor 1). Une fonction nouvelle des RAMP émerge de ces observations, car le complexe RAMP2/R-VPAC1 potentialise la voie de signalisation des phospho-inositides. La régulation de l’expression des RAMP à un niveau transcriptionnel ou post-transcriptionnel revêt une certaine importance, puisqu’elle peut influencer la réponse d’une cellule cible à un ligand, en modifiant le caractère fonctionnel d’un RCPG de classe II ou en affectant le niveau d’une voie de signalisation de ces récepteurs.
Summary
RAMPs (receptor activity-modifying proteins) were discovered in 1998 as accessory proteins needed to the functionnal activity of CGRP (calcitonin gene-related peptide) receptors. Three RAMPs generated by three different genes are known in human, rat and mice. The coding sequences of such genes are described, but as yet, regulation sequences are unknown. RAMPs interact with GPCR (G protein-coupled receptors) of class II. In the case of the calcitonin/CGRP peptide family, RAMPs determine the functionnal specificity of the receptor, glycosylate and translocate the receptor to the cell surface. CGRP receptors are observed in presence of the RAMP1/calcitonin receptor-like receptor (CRLR), but the association of RAMP2 or RAMP3 with CRLR generates an adrenomedullin receptor. The calcitonin receptor (CTR) is translocated alone to the cell surface, but interactions of RAMPs with CTR forms amylin receptors. If RAMPs can interact with glucagon, parathyroid hormone and VIP/PACAP (vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide (VPACR1)) receptors, the functionnal specificity of these receptors remains unaltered. However, the complex VPACR1/RAMP2 enhances specifically the phosphoinoside signaling pathway.
Appendices
Références
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