Engagement of β-arrestin by transactivated insulin-like growth factor receptor is needed for V2 vasopressin receptor-stimulated ERK1/2 activation

• DOI: 10.1073/pnas.1112422109
• Publication Date: 2012-04-10T01:05:20Z
• Authors: Geneviève Oligny-...; Maithé Corbani; Joris Zhou; Mireille Hogue; Gilles Guillon; Michel Bouvier
• Keywords: Arrestin

G protein-coupled receptors (GPCRs) have been shown to activate the mitogen-activated protein kinases, ERK1/2, through both protein-dependent and -independent mechanisms. Here, we describe a protein-independent mechanism that unravels an unanticipated role for β-arrestins. Stimulation of V2 vasopressin receptor (V2R) in cultured cells or vivo rat kidney medullar collecting ducts led activation ERK1/2 metalloproteinase-mediated shedding factor activating insulin-like growth (IGFR). This process was found be Src- β-arrestin–dependent. Whereas Src act upstream metalloproteinase required release IGFR-activating factor, β-arrestins were downstream IGFR transactivation. Unexpectedly, engagement by but not V2R needed promote vasopressin-stimulated activation, indicating pool distinct from those recruited acts tyrosine kinase ERK1/2. Such dual site action helps explain pleiotropic actions this scaffolding protein. Given V2R-stimulated plays cell proliferation, transactivation may important implications renal pathophysiology. Still, event is limited V2R, because observed similar involvement unrelated GPCR (the platelet-activating receptor), it general shared among GPCRs.