Citation:
J Mol Signaling. 2012;7:4 doi:10.1186/1750-2187-7-4
Abstract:
Background PKA, a key regulator of cell signaling, phosphorylates a diverse and important array of target molecules and is spatially docked to members of the A-kinase Anchoring Protein (AKAP) family. AKAR2 is a biosensor which yields a FRET signal in vivo, when phosphorylated by PKA. AKAP5, a prominent member of the AKAP family, docks several signaling molecules including PKA, PDE4D, as well as GPCRs, and is obligate for the propagation of the activation of the mitogen-activated protein kinase cascade from GPCRs to ERK1,2. Results Using an AKAR2-AKAP5 fusion 'biosensor', however we investigated the spatial-temporal activation of AKAP5 undergoing phosphorylation by PKA in response to beta-adrenergic stimulation. The pattern of PKA activation reported by AKAR2-AKAP5 is a more rapid and spatially distinct from those 'sensed' by AKAR2-AKAP12. Spatial-temporal restriction of activated PKA by AKAP5 was found to 'shape' the signaling response. Phosphatase PDE4D tethered to AKAP5 also later reverses within 60 s elevated intracellular cyclic AMP levels stimulated by beta-adrenergic agonist. AKAP12 can 'shape' the temporal and spatial aspects of cell signaling.
Organism or Cell Type:
cell culture: HEK 293