Abstract
G protein-coupled receptors (GPCRs), critical for cellular communication and signaling, represent the largest cell surface protein family and play important roles in numerous pathophysiological processes. Consequently, GPCRs have become a primary focus in drug discovery efforts. Beyond their traditional G protein-dependent signaling pathways, GPCRs are also capable of activating alternative signaling mechanisms, including G protein-independent signaling, biased signaling, and signaling crosstalk. A particularly novel signaling mode employed by these receptors is GPCR transactivation, which enables cross-communication between GPCRs and other receptor types. Intriguingly, GPCR transactivation by distinct GPCRs has also been identified. In this review, I provide an overview of the known GPCR transactivation mechanisms and explore recently uncovered GPCR transactivation mediated by adhesion-class GPCRs (aGPCRs). These aGPCR-GPCR transactivation processes regulate unique cell type-specific functions, offering an exciting opportunity to develop therapies that precisely modulate specific GPCR-mediated biological effects.
Published Version
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