The receptors of the VIP family peptides (VIP, secretin, GRF, PHI, PHM, GIP, glucagon and oxyntomodulin). Specificities and identity.
A model is proposed for the receptors of the VIP family peptides including a ligand and a cellular domain. Specificities of the receptors are due to different ligand binding sites. Three subgroups of the family can be distinguished accordingly: glucagon and oxyntomodulin; GIP; VIP, secretin r and hGRF, PHI and PHM. In the same species, the expression of these different sites is cell-specific resulting in a stoichiometry of the ligand-receptor interaction which is compatible with physiological regulation of cell function. Specificities of the interaction as studied by native and synthetic analogs is supported both by restricted sequences of amino acids (such as that including the N-terminal histidine residue), and membrane-induced configuration of the ligand. Identity of the receptors is related to their interactions with subunits of the adenylate cyclase system. Arguments are put forward indicating that the alpha subunit of the guanyl regulatory protein is a reasonable candidate for directly transducing to the adenylyl cyclase the information contained in the activated ligand-binding site subunits. Evidence of functional and molecular heterogeneity of the recognizing site and of the alpha subunits leads to the supposition that some types of specific complementarity is retained at this level of interaction, further enhancing the possibility of species and cell differences. On the other hand, the identities found in other sequences of the alpha and ras oncogene products extend to the receptor of the VIP family peptides a pattern of organization which is similar to that recently described for the insulin family of receptors. The role of ligand specific receptor mediated regulation in homologous or heterologous desensitization is reviewed in brief for the peptides of the VIP family as well as the appearance of the specific receptor during the ontogenesis or the cell differentiation. The co-distribution of plasma membrane receptors from other families further adds to the cell specificity resulting for each differentiated cell in unique patterns of recognizing site. Some examples of receptor-receptor interaction are given, indicating that the integration of the different signals by cells might occur at an early step through the transmembranair domain of the receptor.
D000818:Animals; D001665:Binding Sites; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D004763:Glucagon-Like Peptides / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D053772:Oxyntomodulin; D010451:Peptide PHI; D010455:Peptides / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D053772:Oxyntomodulin; D010451:Peptide PHI; D010455:Peptides; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D005934:Glucagon; D013007:Growth Hormone-Releasing Hormone