High impact information on Pp2B-14D

• All these results support the hypothesis that Sra regulates female meiosis by controlling calcineurin activity in the germline [1].
• Sra is physically associated with the catalytic subunit of calcineurin, and its overexpression suppresses the phenotypes caused by constitutively activated calcineurin, such as rough eye or loss of wing veins [1].
• Ectopic expression of the homeobox gene Cux-1 rescues calcineurin inhibition in mouse embryonic kidney cultures [2].
• Present results are not compatible with the hypothesis, but suggest that calcineurin inhibits synaptic vesicle recycling [3].
• In this study, we tested a hypothesis that activation of calcineurin, Ca2+/calmodulin-dependent protein phosphatase 2B, is an initiating signal for synaptic vesicle endocytosis [3].

Biological context of Pp2B-14D

• An inhibitory role of calcineurin in endocytosis of synaptic vesicles at nerve terminals of Drosophila larvae [3].
• Hyperactivation of calcineurin signaling in the germline cells resulted in a meiotic-arrest phenotype, which can also be suppressed by overexpression of Sra [1].

Associations of Pp2B-14D with chemical compounds

• We examined effects of calcineurin inhibitors, cyclosporin A or FK506 and calmodulin inhibitors on stimulus-induced FM1-43 uptake into nerve terminals of Drosophila larvae [3].
• Pretreatment with rapamycin (2 or 20 microM), a structural analog of FK506 which has no effect on calcineurin, or calyculin A (0.3-50 nM), an inhibitor of protein phosphatase 1 and 2A, had no detectable effect on FM1-43 uptake [3].

Other interactions of Pp2B-14D

• In resting cells, NFAT proteins are heavily phosphorylated and reside in the cytoplasm; in cells exposed to stimuli that raise intracellular free Ca2+ levels, they are dephosphorylated by the calmodulin-dependent phosphatase calcineurin and translocate to the nucleus [4].

Analytical, diagnostic and therapeutic context of Pp2B-14D

• The PCR analyses also point to the presence in Drosophila and mammals of three or more different genes encoding PP2B, the enzyme recently identified as the target of certain immunosuppressant drugs [5].

References