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

Curr Biol. 2000 Apr 6;10(7):409-12. doi: 10.1016/s0960-9822(00)00419-x.


Phosphorylation of G-protein-coupled receptors by second-messenger-stimulated kinases is central to the process of receptor desensitization [1-3]. Phosphorylation of the beta(2)-adrenergic receptor (beta(2)-AR) by protein kinase A (PKA), in addition to uncoupling adenylate cyclase activation, is obligatory for receptor-mediated activation of mitogen-activated protein kinase (MAP kinase) cascades [4] [5]. Although mechanisms for linking G-protein-coupled receptor kinases to the activated receptor are well established, analogous 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-kinase-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 receptor phosphorylation following agonist stimulation. Functional studies show 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 signaling enzymes to a G-protein-coupled receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing*
  • Adrenergic beta-2 Receptor Agonists
  • Animals
  • Brain
  • Calcineurin
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • GTP-Binding Proteins / metabolism
  • MAP Kinase Signaling System*
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Rats
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Signal Transduction


  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing
  • Adrenergic beta-2 Receptor Agonists
  • Akap5 protein, rat
  • Carrier Proteins
  • Receptors, Adrenergic, beta-2
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin
  • GTP-Binding Proteins