GSK3/shaggy-like genes encode kinases that are involved in a variety of biological processes. By functional complementation of the yeast calcineurin mutant strain DHT22-1a with a NaCl stress-sensitive phenotype, we isolated the Arabidopsis cDNA AtGSK1, which encodes a GSK3/shaggy-like protein kinase. AtGSK1 rescued the yeast calcineurin mutant cells from the effects of high NaCl. Also, the AtGS...

Cyclosporin A (CsA) and FK506 are antimicrobial, immunosuppressive natural products that inhibit signal transduction. In T cells and Saccharomyces cerevisiae, CsA and FK506 bind to the immunophilins cyclophilin A and FKBP12 and the resulting complexes inhibit the Ca2+-regulated protein phosphatase calcineurin. We find that growth of the opportunistic fungal pathogen Cryptococcus neoformans is s...

Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, a...

Calcineurin is a calcium-calmodulin-regulated, serine-threonine phosphatase that functions as a key inducer of stress responsive gene expression in multiple cell types through a direct activation of nuclear factor of activated T cells and myocyte enhancer factor 2 transcription factors. In cardiomyocytes, calcineurin signaling has been implicated in the regulation of the hypertrophic response c...

Two Ca2+-dependent signaling pathways, mediated by the Ca2+-activated phosphatase calcineurin and by the Ca2+-activated kinase Ca2+/calmodulin-dependent kinase (CaMK), are both believed to function in fast-to-slow skeletal muscle fiber type transformation, but questions about the relative importance of the two pathways still remain. Here, the differential gene expression during fast-to-slow fib...

We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants that inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B). A single nuclear mutation, designated cev1 for calcineurin essential for viability, is responsible for the CsA-FK506-sensitive phenotype. The peptidyl-prolyl cis-trans isomerases cyclo...

The calcium-responsive molecule, calcineurin, has been well characterized to play a causal role in pathological cardiac hypertrophy over the past decade. However, the intrinsic negative regulation of calcineurin signaling during the progression of cardiomyocyte hypertrophy remains enigmatic. Herein, we explored the role of EPI64C, a dual inhibitor of both Ras and calcineurin signaling during T-...

Aspergillus fumigatus is an aggressive opportunistic pathogen of humans as well as a major allergen. Environmental sensing and retrieving essential nutrients from the environment are general metabolic traits associated with the growth of this saprophytic fungus. Two important mediators of calcium signals in eukaryotic cells are the Ca(2+)-binding protein calmodulin and the Ca(2+)/calmodulin-dep...

It is well known that angiotensin II (Ang II) is implicated in the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs). To study the mechanisms by which Ang II contributes to the pathological changes of VSMCs, we examined whether Ang II stimulated myocyte enhancer factor 2 (MEF2)- and calcineurin/nuclear factor of activated T cell (NFAT)-dependent transcriptional activ...

The calcium-dependent phosphatase calcineurin and its downstream transcriptional effector nuclear factor of activated T cells (NFAT) are important regulators of inducible gene expression in multiple cell types. In T cells, calcineurin-NFAT signaling represents a critical event for mediating cellular activation and the immune response. The widely used immunosuppressant agents cyclosporin and FK5...