Molecular mechanisms involved in vasoactive intestinal peptide receptor activation and regulation: current knowledge, similarities to and differences from the A family of G-protein-coupled receptors

Abstract

An actual paradigm for activation and regulation of the GPCR (G-protein-coupled receptors)/seven-transmembrane helix family of receptors essentially emerges from extensive studies of the largest family of receptors, the GPCR-A/rhodopsin family. The mechanisms regulating the GPCR-B family signal transduction are less precisely understood due in part to the lack of the conserved signatures of the GPCR-A family (E/DRY, NPXXY) and in part to the absence of a reliable receptor modelling, although some studies suggest that both families share similar features. Here, we try to highlight the current knowledge of the activation and the regulation of the VIP (vasoactive intestinal peptide) receptors, namely VPAC (VIP/pituitary adenylate cyclase-activating peptide receptor) 1 and 2. This includes search for amino acids involved in the stabilization of the receptor active conformation and in coupling to G-proteins, signalling pathways activated in response to VIP, agonist-dependent receptor down-regulation, phosphorylation and internalization as well as pharmacological consequences of receptor hetero-dimerization.

Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

“…VIP exerts its actions through two structurally related Gprotein-coupled receptor B family members, VPAC1 and VPAC2 (44). One or both of these receptors are expressed on a wide range of cell types, including neuronal, epithelial, smooth muscle, and immune cells (e.g., T cells, macrophages, monocytes, dendritic cells, and polymorphonuclear cells) (22).…”

Physiology of Microglia

“…496). The activation of these receptors is known to trigger anti-inflammatory and immunodepressive responses in various peripheral tissues (e.g., Refs.…”

Evidence that Interaction between Conserved Residues in Transmembrane Helices 2, 3, and 7 Are Crucial for Human VPAC1 Receptor Activation

“…Considering the VPAC 1 receptor as a paradigm for class B, it actually seems that a large network of interactions must be considered. Indeed, on the basis of mutagenesis studies, it has been proposed that TM1, TM2, TM3, and TM6 and the intracellular loop 3 and the proximal part of the C-terminal intracytoplasmic tail take part in the receptor signal transduction (Gaudin et al, 1998(Gaudin et al, , 1999Couvineau et al, 2003;Langer and Robberecht, 2007).…”