A-kinase anchoring proteins (AKAPs) function to sequester the cAMP dependent protein kinase, PKA, to specific subcellular locations. In addition, AKAPs function as adapters that assemble multi-protein complexes that include signal termination enzymes such as phosphodiesterases (PDEs) and phosphatases. This compartmentalization of PKA in close proximity to targets and other enzymes contributes to the specificity of cAMP-mediated signaling. Previous studies in the Scott lab have indicated that the muscle-selective anchoring protein mAKAP assembles a cAMP-signaling module of PKA and a cAMP-selective phosphodiesterase PDE4D3 to locally regulate PKA activity in cardiac muscle. More recent unpublished data indicates that the mitogen activated protein kinase, EKR5 and its upstream effector, MEK5, are also present in the mAKAP-signaling complex. Therefore the specific l aims of this proposal are to 1) functionally characterize the ERK5 / mAKAP interaction and 2) identify other EKR5 substrates and proteins within the mAKAP signaling complex.
| Goehring, April S; Pedroja, Benjamin S; Hinke, Simon A et al. (2007) MyRIP anchors protein kinase A to the exocyst complex. J Biol Chem 282:33155-67 |
