Gα₁₂ facilitates shortening in human airway smooth muscle by modulating phosphoinositide 3-kinase-mediated activation in a RhoA-dependent manner.

ABSTRACT:

Background and purpose

PI3K-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given that G₁₂ family proteins activate ROCK pathways in other cell types, their role in M₃ muscarinic acetylcholine receptor-stimulated PI3K/ROCK activation and contraction was examined.

Experimental approach

Gα₁₂ coupling was evaluated using co-immunoprecipitation and serum response element (SRE)-luciferase reporter assays. siRNA and pharmacological approaches, as well as overexpression of a regulator of G-protein signaling (R

SUBMITTER: Yoo EJ 

PROVIDER: S-EPMC5715591 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature