Calcineurin

Abstract

The serine/threonine phosphatase calcineurin acts as a crucial connection between calcium signaling the phosphorylation states of numerous important substrates. These substrates include, but are not limited to, transcription factors, receptors and channels, proteins associated with mitochondria, and proteins associated with microtubules. Calcineurin is activated by increases in intracellular calcium concentrations, a process that requires the calcium sensing protein calmodulin binding to an intrinsically disordered regulatory domain in the phosphatase. Despite having been studied for around four decades, the activation of calcineurin is not fully understood. This review largely focuses on what is known about the activation process and highlights aspects that are currently not understood.

Specific disruption of calcineurin-signaling in the distal convoluted tubule impacts the transcriptome and proteome, and causes hypomagnesemia and metabolic acidosis

“…Our results demonstrate a striking effect of CnB1 deletion on the transcriptome and proteome of DCT cells. Calcineurin and its inhibitors are known to impact on gene transcription via dephosphorylation of several transcription factors including NFAT and by interfering with the MAPK pathway 4,5 .…”

“…Moreover, calcineurin or its inhibitors are thought to impact several additional signal transduction pathways including other transcription factors (e.g. forkhead transcription factors, myocyte-specific enhancer factor 2, transcription factor EB) and the mitogen activated protein kinase (MAPK) 4,5 .…”

Calmodulin and Its Binding Proteins in Parkinson’s Disease

“…CaN is highly expressed in the mammalian brain, especially in neurons [ 73 ]. It is built of a catalytic subunit (CaNA) and a Ca 2+ -binding regulatory subunit (CaNB) [ 74 ]. CaNA contains an autoinhibitory domain and CaM-binding site.…”

In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

“…Calcineurin (CaN, also called protein 2B phosphatase, PP2B) is the main binding enzyme to the multifunctional protein calmodulin (CaM) in the brain and the only serine/threonine phosphatase under the control of Ca 2+ /CaM, playing a critical role in Ca 2+ -mediated cellular responses [13][14][15][16]. Stimulation of CaN by CaM ensures the coordinated regulation of its phosphatase function with the activities of many other enzymes, including Ca 2+ and CaM control-dependent kinases.…”