Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth and stress are generally incompatible states. Stressed cells adapt to an insult by restraining growth, and conversely, growing cells keep stress responses at bay. This is evident in many physiological settings, including for example, the effect of stress on the immune or nervous system, but the underlying signaling mechanisms mediating such mutual antagonism are poorly understood. In eukaryotes, a central activator of cell growth is the protein kinase target of rapamycin (TOR) and its namesake signaling network. Calcineurin is a conserved, Ca(2+)/calmodulin-dependent protein phosphatase and target of the immunosuppressant FK506 (tacrolimus) that is activated in yeast during stress to promote cell survival. Here we show yeast mutants defective for TOR complex 2 (TORC2) or the essential homologous TORC2 effectors, SLM1 and SLM2, exhibited constitutive activation of calcineurin-dependent transcription and actin depolarization. Conversely, cells defective in calcineurin exhibited SLM1 hyperphosphorylation and enhanced interaction between TORC2 and SLM1. Furthermore, a mutant SLM1 protein (SLM1(DeltaC14)) lacking a sequence related to the consensus calcineurin docking site (PxIxIT) was insensitive to calcineurin, and SLM1(Delta)(C14) slm2 mutant cells were hypersensitive to oxidative stress. Thus, TORC2-SLM signaling negatively regulates calcineurin, and calcineurin negatively regulates TORC2-SLM. These findings provide a molecular basis for the mutual antagonism of growth and stress.
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PMID:Mutual antagonism of target of rapamycin and calcineurin signaling. 1695 79

The yeast proteins, Msb3p and Msb4p, are two Ypt/Rab-specific GTPase-activating proteins sharing redundant functions in exocytosis, organization of the actin cytoskeleton, and budding site selection. To see if Msb3p might play an additional, specific role, we first tested the sensitivities of msb3 and msb4 mutant strains to different drugs and then screened a genomic library for multicopy suppressors of msb3 sensitivity to CdCl(2) or to the calcium channel blocker diltiazem hydrochloride. Three genes (ADH1, RNT1, and SUI1) were found to suppress the CdCl(2) sensitivity of the msb3 strain and three others (YAP6, ZEO1, and SLM1) its diltiazem-HCl sensitivity. The results suggest a possible involvement of Msb3p in calcineurin-mediated signalling.
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PMID:Multicopy suppression screen in a Saccharomyces cerevisiae strain lacking the Rab GTPase-activating protein Msb3p. 2087 64