The importance of three conserved transmembrane prolines of the human vasoactive intestinal polypeptide (VPAC)1 receptor was examined by single alanine substitution. P266A, P300A and P348A reduced the expression level, but maintained the binding to VIP. P266A showed decreased ability to stimulate cAMP, while P300A and P348A displayed an increased potency in cAMP production combined with a high sensitivity towards GTP compared to the wild type receptor. In addition, substitutions of two conserved leucines located in position -2 and +1 from P348 were investigated. L346A and L349A reduced the receptor expression, influenced the G protein coupling and decreased the receptor activity. These observations, which are the first on conserved transmembrane prolines within this family of receptors, indicate that these residues are important for receptor expression, G protein coupling and receptor activity. © 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
Knudsen, S. M., Tams, J. W., & Fahrenkrug, J. (2001). Functional roles of conserved transmembrane prolines in the human VPAC1 receptor. FEBS Letters, 503(2–3), 126–130. https://doi.org/10.1016/S0014-5793(01)02716-8