Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling

Phosphorylation of G-protein-coupled receptors by second-messenger-stimulat ed kinases is central to the process of receptor desensitization [1-3]. Pho sphorylation of the beta(2)- adrenergic receptor (beta(2)-AR) by protein ki nase A (PKA), in addition to uncoupling adenylate cyclase activation, is ob ligatory for receptor-mediated activation of mitogen-activated protein kina se (MAP kinase) cascades [4,5]. Although mechanisms for linking G-protein-c oupled receptor kinases to the activated receptor are well established, ana logous mechanisms for targeting second messenger kinases to the beta(2)-AR at the plasma membrane have not been elucidated. Here we show that the A-ki nase-anchoring protein, AKAP79/150, co-precipitates with the beta(2)-AR in cell and tissue extracts, nucleating a signaling complex that includes PKA, protein kinase C (PKC) and protein phosphatase PP2B. The anchoring protein directly and constitutively interacts with the beta(2)-AR and promotes rec eptor phosphorylation following agonist stimulation. Functional studies sho w that PKA anchoring is required to enhance beta(2)-AR phosphorylation and to facilitate downstream activation of the MAP kinase pathway. This defines a role for AKAP79/150 in the recruitment of second-messenger regulated sig naling enzymes to a G protein-coupled receptor. (C) 2000 Elsevier Science L td. All rights reserved.