Abstract
Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years, calcineurin has been the subject of extensive investigation. Many of its cellular and physiological functions have been described, and the underlying biophysical mechanisms are the subject of active investigation. With the abundance of techniques and experimental designs utilized to study calcineurin and its numerous substrates, it is difficult to reconcile the available information. There have been a plethora of reports describing the role of calcineurin in cardiac disease. However, a physiological role of calcineurin in healthy cardiomyocyte function requires clarification. Here, we review the seminal biophysical and structural details that are responsible for the molecular function and inhibition of calcineurin. We then focus on literature describing the roles of calcineurin in cardiomyocyte physiology and disease.
Highlights
Calcineurin, known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways
In 1976, Wang et al demonstrated that bovine brain cyclic nucleotide phosphodiesterase required a higher concentration of a “calcium regulated protein modulator” (one of the original names for the calcium (Ca2+ ) sensing protein calmodulin) for activation in brain tissue compared to heart tissue
Β phosphorylase kinase phosphatase is known as protein phosphatase 1 glycogenassociated regulatory subunit, or protein phosphatase type-1 glycogen targeting subunit [4]
Summary
In 1976, Wang et al demonstrated that bovine brain cyclic nucleotide phosphodiesterase (likely PKA and/or PKG) required a higher concentration of a “calcium regulated protein modulator” (one of the original names for the calcium (Ca2+ ) sensing protein calmodulin) for activation in brain tissue compared to heart tissue This was due to the presence of an “inhibitory factor” (CaN) in the brain preparations that counteracted the activation of the phosphodiesterase (Figure 1) [2]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations Both PP2A and PP2B (CaN) can dephosphorylate the α and β subunits of phosphorylase kinase; there are enzymatic differences between these two proteins. PP2B is more specific in its substrate selection, and dephosphorylates the phosphorylase kinase α subunit more rapidly (100 fold) compared to the β subunit [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
