AKAP Phosphatase Complexes in the Heart

Abstract

Directed protein phosphorylation is indisputably critical for a multitude of cellular processes. A growing body of research demonstrates A Kinase Anchoring Proteins (AKAPs) to mediate a significant number of phosphorylation events in the heart. By acting as molecular tethers for the regulatory subunit of PKA, AKAPs focus the kinase's actions onto specific substrates. In the time since their discovery, the AKAP model has evolved in appreciation of the broader role these scaffolds play in coordinating multiple signaling enzymes in order to efficiently regulate dynamic cellular processes. The focus of this review is on the emerging role of AKAPs in regulating the three main cardiac phosphatases: Protein Phosphatase 1 by AKAP18 and Yotiao, and Protein Phosphatases 2A and 2B by mAKAP.

Influence of phosphodiesterases and cGMP on cAMP generation and on phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in porcine left atrium

“…Sustained TnI and PLB phosphorylation could be due to limited access by protein phosphatases (PP) or continued phosphorylation by PKA. PLB and TnI have been reported to be dephosphorylated by PP1 and PP2A which, like PKA, are tightly regulated and compartmentalized by binding to scaffolding proteins (Redden and Dodge-Kafka 2011). Taken together, our results suggest that the inotropic mechanisms initiated by 5-HT fade quickly with the decline in cAMP, while the lusitropic effects are sustained as also reported in De Maeyer et al (2006), due to maintained phosphorylation of TnI and PLB.…”

Acute β-Adrenergic Activation Triggers Nuclear Import of Histone Deacetylase 5 and Delays Gq-induced Transcriptional Activation

“…It has also been suggested that ISO can induce nuclear HDAC5 export via a PKA-independent but oxidationdependent pathway in adult rat myocytes (42). The discrepancies could be due to the nature of different cell types (they used HEK and cultured neonatal/adult rat ventricular myocytes) and the respective 14-3-3 isoforms present to associate with HDACs (21,43,44) Additionally, substrate specificity of cAMP/PKA signaling is achieved by compartmentalization of localized cAMP gradient via phosphodiesterase isoforms or ␤-arrestins and by association with various AKAP scaffolding subtypes in different cell types (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). Our study provides real-time observation of HDAC5-GFP translocation in adult myocytes to more accurately reflect the fundamentally dominant endogenous signaling pathway in adult ventricular myocytes.…”

A Protein Kinase A–Independent Pathway Controlling Aquaporin 2 Trafficking as a Possible Cause for the Syndrome of Inappropriate Antidiuresis Associated with Polycystic Kidney Disease 1 Haploinsufficiency

“…Calyculin-A is a strong phosphatase inhibitor displaying effect on PP2A (IC 50 approximately 0.5-1 nM) and less effect on PP1 (IC 50 approximately 2 nM), two phosphatases sharing some degree of redundancy. 29,30 To reach a specific Figure 6. Effect of R-roscovitine on protein phosphatase expression and activity in MDCK-hAQP2 cells.…”