Genetic evidence that β-arrestins are dispensable for the initiation of β₂-adrenergic receptor signaling to ERK.

ABSTRACT: The β₂-adrenergic receptor (β₂AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β₂AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β₂AR internalization. Unexpectedly, β-arr1 and β-arr2 and receptor internalization were dispensable for ERK activation. Instead, β₂AR signaled through Gα_s and Gβγ subunits through a pathway that involved the tyrosine kinase SRC,

SUBMITTER: O'Hayre M 

PROVIDER: S-EPMC5751434 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature