ArticleCell & bioscience2026
Finding functional gaps: integrative analysis of VPAC1- and VPAC2-mediated signalling pathways in human lymphocytes.
Article in Cell & bioscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundVasoactive Intestinal Peptide (VIP) is a pleiotropic neuropeptide regulating diverse cellular and physiological processes. Its functions are primarily mediated through two G protein-coupled receptors, VPAC1 and VPAC2. The aim of this study was to perform an integrative analysis of VPAC receptor signalling, encompassing receptor-G protein coupling, second messenger production, kinase activation and transcriptional responses in T cells. EXPERIMENTAL APPROACH: Receptor interactions with Gα subunits were analysed using BRET assays. Stable Jurkat T-cell lines overexpressing VPAC1 (J-OEV1) or VPAC2 (J-OEV2) were generated. VPAC-dependent intracellular signalling in these cells was assessed by measuring cAMP and Ca
resultsVPAC1 showed interaction with both Gαs and Gαq subunits, whereas VPAC2 preferentially interacted with Gαs. In Jurkat cells, both receptors overexpression enhanced cAMP signalling, while increased Ca
conclusionThis study aimed to identify functional differences between VPAC1 and VPAC2 signalling and reveals reproducible subtype-specific differences at early signalling. In Jurkat cells, both receptors induce a shift in its basal state; however, changes do not persist during TCR-driven activation, resulting in largely convergent effector responses.
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