Kinase Anchoring Proteins as the Basis for cAMP Signaling

Contents

1 Introduction 4

1.1 Compartmentation of cAMP Signaling 4

2 AKAPs 5

3 Discovery of AKAP Function 6

4 mAKAP as a Model for the Regulation of cAMP Signaling 7

5 AKAPs as Drug Targets 10

6 Future Directions 12

References 12

Abstract Common challenges to any cell are the processing of the extracellular stimuli it receives into intracellular signaling cascades that initiate a multitude of diverse biological functions. However, many of these stimuli act via a common signaling pathway, suggesting the cell must somehow discriminate between different stimuli and respond accordingly. Subcellular targeting through the association with adaptor and scaffolding proteins has emerged as a key mechanism by which cells maintain signaling specificity. Compartmentation of cAMP signaling is maintained by the clustering of cAMP signaling enzymes in discrete units by the scaffolding protein A-kinase anchoring proteins (AKAP). In doing so, AKAPs provide the molecular architecture for the cAMP micordomains that underlie the spacial-temporal control of cAMP signaling.

Abbreviations PKA: cAMP-dependent protein kinase; C: PKA catalytic subunit; RI: PKA regulatory subunit type I; RII: PKA regulatory subunit type II; AKAP: A-kinase anchoring protein; PDE: Phosphodiesterase; RyR: Ryanodine receptor; PP2A: Protein phosphatase 2A; Epac: Exchange protein activated by cAMP

K.L. Dodge-Kafka

Pat and Jim Calhoun Center for Cardiology, Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030, USA [email protected]

E. Klussmann, J. Scott (eds.) Protein-Protein Interactions as New Drug Targets. Handbook of Experimental Pharmacology 186, © Springer-Verlag Berlin Heidelberg 2008

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