A novel noncanonical signaling pathway for the μ-opioid receptor.

ABSTRACT: The µ-opioid receptor (OPRM1) signals as a classic G protein-coupled receptor by activating heterotrimeric Gi/Go proteins resulting in adenylyl cyclase (AC) inhibition. Such AC inhibition is desensitized after prolonged agonist treatment. However, after receptor desensitization, the intracellular cAMP level remains regulated by OPRM1, as demonstrated by the intracellular cAMP level increase or AC superactivation upon removal of an agonist or addition of an antagonist. We now demonstrate that such intracellular cAMP regulation is mediated by a novel noncanonical signaling pathway resulting from OPRM1 being converted to a receptor tyrosine kinase (RTK)-like entity. This noncanonical OPRM1 signaling is initiated by the receptor recruiting and activating Src kinase within the receptor complex,

SUBMITTER: Zhang L 

PROVIDER: S-EPMC3834144 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature