Endocytosis drives active cAMP signal discrimination among natively co-expressed GPCRs.

ABSTRACT: Many G protein-coupled receptors (GPCRs) initiate a second phase of signaling after activation-induced endocytosis, but GPCRs vary considerably in their ability to internalize when activated. Here we show that this fundamental trafficking difference distinguishes the downstream signaling profiles of natively co-expressed GPCRs through the cAMP cascade. We focus on signaling to the nucleus stimulated by three different Gs-coupled GPCRs that are each endogenously co-expressed in human embryonic kidney cells but differ in their ability to internalize after activation: the adenosine-2B receptor that does not detectably internalize, the vasoactive intestinal peptide receptor-1 that internalizes very rapidly, and the β2-adrenergic receptor that internalizes less rapidly. We show that each GPCR p

SUBMITTER: Blythe EE 

PROVIDER: S-EPMC12262454 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature