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Review
. 2010 Mar 16;121(10):1264-71.
doi: 10.1161/CIRCULATIONAHA.109.896357.

A-kinase anchoring proteins: getting to the heart of the matter

John D Scott  1 , Luis F Santana
Affiliations
Review

A-kinase anchoring proteins: getting to the heart of the matter

John D Scott et al. Circulation. .
No abstract available

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Figures

Figure 1
Figure 1. Schematic diagram of the role of AKAPs in Excitation-Contraction coupling in cardiomyocytes
a) Phase 1 of EC coupling: AKAP79/150 and the short forms of AKAP15/18 (α and β) maintain signaling complexes tethered to L-type calcium channels to enable calcium influx. b) Phase 2 of EC coupling: Ryanodine receptors at the sarcoplasmic reticulum are bound to the mAKAP signaling complex as it responds to the increased cytosolic Ca++. mAKAP clusters PKA, PDE4D3 and PP2A to regulate the phosphorylation status of the Ryr and the resultant Ca++ release from the SR. c) Phase 3 of EC coupling: Active transport of calcium back into the SR via SERCA2 is regulated by phospholamban. The AKAP15/18δ long isoform brings PKA into complex with phospholamban and SERC2 where it can augment the phosphorylation of phospholamban and the reuptake of calcium into the SR.
Figure 2
Figure 2. Schematic diagram of Yotiao and Iκs currents
a) In myocytes Yotiao associates with the KCNQ1 subunit of the Iκs potassium channel. Anchored PKA phosphorylation of Yotiao enhances activation of the channel. b) The S1570L Yotiao mutant has reduced interaction with KCNQ1 and delayed repolarization of ventricular action potential.
Figure 3
Figure 3. Schematic diagram of the role of AKAPs in transcriptional regulation in the heart
a) An upregulation of AKAP-Lbc facilitates PKD activation and phosphorylation of HDAC5, leading to transcriptional activation of the MEF pathway and the onset of hypertrophy. b) Calcium mediated activation of AKAP150-targeted PP2B leads to dephosphorylation of NFATc3 in arterial myocytes. Dephosphorylated NFATc3 accumulates in the nucleus where it leads to decreased gene expression of channel subunits. c) mAKAP organizes ubiquitin E3 ligases that managed the stability of the transcription factor HIF-1α During hypoxia, HIF1α translocated to the nucleus initiates transcription of proangiogenic, metabolic, and antiapoptotic genes that promote cell survival during hypoxia.
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