Systematic Quantification of GPCR/cAMP-Controlled Protein Kinase A
                    Interactions

O. Torres-Quesada; R. Röck; E. Stefan

doi:10.1055/s-0042-110791

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2017; 49(04): 240-249
DOI: 10.1055/s-0042-110791

Review

Systematic Quantification of GPCR/cAMP-Controlled Protein Kinase A Interactions

O. Torres-Quesada^*

¹Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria

,

R. Röck^*

¹Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria

,

E. Stefan

¹Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria

› Author Affiliations

Abstract

The diffusible second messenger cyclic AMP (cAMP) originates from multiple G protein-coupled receptor (GPCR) cascades activating the intracellular key effector protein kinase A (PKA). Spatially and temporally restricted cAMP-fluxes are directly sensed by macromolecular PKA complexes. The consequences are alterations of molecular interactions, which lead to activation of compartmentalized PKA phosphotransferase activities, regulating a vast array of cellular functions. To decode cell-type and cell-compartment specific PKA functions, the spatio-temporal dynamics of small molecule:protein interactions, protein:protein interactions (PPIs), cAMP-mobilization, and phosphotransferase activities need to be determined directly in the appropriate cellular context. A collection of cell-based reporters has been developed to either visualize or quantitatively measure kinase activities or PKA complex formation/dissociation. In this review, we list a collection of unimolecular and bimolecular PKA biosensors, followed by the specification of the modular design of a Renilla luciferase based protein-fragment complementation assay (PCA) platform for measuring PKA network interactions. We discuss the application spectrum of the PCA reporter to identify, quantify, and dissect dynamic and transient PKA complexes downstream of specific GPCR activities. We specify the implementation of a PCA PKA platform to systematically quantify the concurrent involvement of receptor-cAMP signaling, post-translational modifications, and kinase subunit mutations/perturbations in PKA activation. The systematic quantification of transient PKA network interactions will contribute to a better understanding how GPCR-recognized input signals are streamlined through the compartmentalized and cAMP-interacting PKA signalosome.

Key words

molecular interactions - post-translational modifications - biosensor - PPI reporter - signal transduction - signaling crosstalk

Full Text

References

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