Protein Phosphatase 2B Calcineurin

The A kinase anchor proteins (AKAP), which are tightly associated with the cytoskeleton, serve as anchors for protein kinase A. In addition to the RII subimit of protein kinase A, the AKAP proteins also bring protein phosphatases and other protein kinases to the cytoskeleton in a targeted fashion. The AKAP79 protein binds protein kinase C and protein phosphatase 2B (calcineurin) as well as the RII subunit. The possibility to bring both a protein kinase and a protein phosphatase to the same place in the cell opens up the prospect of a coordinated and layered regulation of both enzyme activities. 

Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G (2001) Chemokines and their receptors in the central nervous system. Front Neuroendocrinol 22 147-184 Bales JW, Ma X, Yan HQ, Jenkins LW, Dixon CE (2010) Expression of protein phosphatase 2B (calcineurin) subunit A isoforms in rat hippocampus after traumatic brain injury. J Neurotrauma 27 109-120... 

Protein phosphatase 2B, also called calcineurin, is a Ca27calmodulin-activated enzyme composed of two major subunits the A subunit contains the catalytic activity and is highly homologous to PP1, and the B subunit... 

Protein phosphatase 2B is also known as calcineurin. Calcineurin is made up of a catalytic A subunit and a regulatory B subimit that shows similarity to calmodulin. A binding site for Ca Vcalmoduhn, required for activation of calcineurin, is found in the catalytic subunit. 

Renewed docking of the catalytic subunit requires the removal of the phosphate residue at the G subunit phosphorylated at the P2 site. This takes place via the protein phosphatases 2A and 2B (calcineurin). Thus, a cascade of protein phosphatases is involved in the regulation of dephosphorylation of key enzymes of glycogen degradation, whereby a phosphatase, namely protein phosphatase I, is indirectly activated by other protein phosphatases. With calcineurin, a Ca -dependent protein phosphatase is involved and thus it is possible to influence glycogen metabolism via Ca -mediated signals. 

Calcineurin is the serine/threonine protein phosphatase 2B. It binds calmodulin and its activity is regulated by Ca +. ... 

Fenvalerate has low toxicity in mammals due to its rapid metabolic breakdown. It acts directly on nerve axons by prolonging sodium channel opening in cell membranes. Insects exposed to fenvalerate are quickly paralyzed exposure causes quick insect knockdown. In small animals, type II pyrethroids cause salivation, chewing, burrowing, choreoathetosis, and seizures. They also cause lower action potential amplitude, marked membrane depolarization, and eventual total neural activity blockade. Fenvalerate is likely to act both on peripheral and central nervous system. It is also a potent inhibitor of calcineurin (protein phosphatase 2B). 

Calcineurin (protein phosphatase 2B) is a Ser/Thr phosphatase that is controlled by cellular calcium and regulates a large number of biological responses including lymphocyte activation, neuronal and muscle development, and the development of vertebrate heart valves. 

Such exogenous inhibitors, however, may also be of great benefit as was found to be the case for the cyclic peptide cyclosporin A and the macrolide FK506 from fungal origin, which are excellent inhibitors of calcineurin, the protein phosphatase 2B... 

Li, Z., Okamoto, K., Hayashi, Y. and Sheng, M. 2004b. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119 873-887 Li, G., Yin, H. and Kuret, J. 2004c. Casein kinase 16 phosphorylates tau and disrupts its binding to microtubules. J. Biol. Chem. 279 15938-15945 Lian, Q., Ladner, C.J., Magnuson, D. and Lee, J.M. 2001. Selective changes of calcineurin (protein phosphatase 2B) activity in Alzheimer s disease cerebral cortex. Exp. Neurol. 167 158-165... 

In mammals, at least eight types of Ser/Thr-specific protein phosphatases have been identified, and these are classified according to their substrate specificities, metal requirements, and sensitivities to natural or synthetic inhibitors. Four groups of the Ser/ Thr phosphatases, the protein phosphatases (PP) 1, 2A, 2B and C2, have been studied in detail. PP-1, PP-2A and PP-2B, which is also known as calcineurin, are highly homo-... 

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