title: G-protein-coupled receptor-associated A-kinase anchoring proteins AKAP5 and AKAP12: differential signaling to MAPK and GPCR recycling.
abstract: BACKGROUND
  A-kinase Anchoring Protein AKAP5 and AKAP12 both dock to the beta2-adrenergic receptor, the former constitutively, the latter dynamically in response to activation of the receptor with agonist.
  
  
  RESULTS
  In the current work we analyze the ability of each AKAP to contribute to two downstream signaling events, the activation of mitogen-activate protein kinase and the resensitization/recycling of the internalized, desensitized beta2-adrenergic receptor to the cell membrane. Although both AKAP share a large number of docking partners in common (e.g., beta2-adrenergic receptor, protein kinases A and C, protein phosphatase-2B, and negatively-charged membrane phospholipids), AKAP5 and AKAP12 are shown to segregate with respect to activation of Erk1,2 and to resensitization/recycling of beta2-adrenergic receptor. A431 cells were found to highly express AKAP12, but little of AKAP5. HEK293 cells, in contrast, were found to highly express AKAP5, but little of AKAP12. Suppression of the expression of AKAP5 in either A431 cells or HEK293 cells leads to loss of the ability of the beta2-adrenergic receptor to activate Erk1,2. Suppression of the expression of AKAP12 in either cell line leads to loss of the ability of these cells to resensitize the beta2-adrenergic receptor.
  
  
  CONCLUSIONS
  Knock-down experiments of endogenous AKAP 5 and AKAP12 in two cell lines used commonly to study beta2-adrenergic receptor signaling clearly discriminate between the activation of mitogen-activated protein kinase (a downstream read-out solely mediated by AKAP5) and receptor recycling (a downstream read-out solely mediated by AKAP12).
authors.affiliation: Department of Pharmacology, School of Medicine, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA. craig@pharm.stonybrook.edu.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Tao
authors.forename: Craig C
authors.initials: CC
authors.lastname: Malbon