When 6 is 9: 'Uncoupled' AT1 receptors turn signalling on its head

Abstract

The type 1 angiotensin receptor (AT1) activates an array of intracellular signalling pathways that control cell and tissue responses to the peptide hormone angiotensin II (AngII). The capacity of AT1 receptors to initiate and maintain such signals has typically been explained on the basis of conventional heterotrimeric guanine nucleotide binding protein (G protein) activation, specifically Gq/11. Accumulating evidence from studies utilising a variety of AT1 receptor mutants and AngII analogues indicates that some important downstream effects of AT1 receptors are independent of classical G protein coupling. Importantly, AT1 receptor-mediated endocytosis, tyrosine phosphorylation signalling an..