PubMed · 10200239
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A Trewavas. 1999-04-13. How plants learn.. https://doi.org/10.1073/pnas.96.8.4216
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Calcineurin is a phosphatase with activity dependent on both Ca(2+)/calmodulin binding to the catalytic A subunit and Ca(2+) binding to the regulatory B subunit. We have previously shown that Pb(2+) activates calmodulin with a threshold of about 100 pM free Pb(2+), and that Pb(2+) and Ca(2+) are roughly additive in calmodulin activation (Kern et al., NeuroToxicology 21, 353-364 (2000)). In the present study, we evaluated the effects of Pb(2+), with and without Ca(2+) and calmodulin, on calcineurin activity. In calmodulin-containing, Ca(2+)-free solutions, Pb(2+) activated calcineurin with a threshold of about 100 pM free Pb(2+). Maximum calcineurin activity (comparable to that induced by 10 microM Ca(2+)) was reached at about 200 pM free Pb(2+). Higher Pb(2+) concentrations reduced activity, although some activity remained even at 2000 pM free Pb(2+). Combined with subsaturating Ca(2+) concentrations, as little as 20 pM free Pb(2+) enhanced calcineurin activity, but free Pb(2+) concentrations greater than 200 pM still reduced activity below maximum. Extremely high Ca(2+) concentrations (10 microM) completely reversed the inhibition of activity by 2000 pM free Pb(2+). In the absence of calmodulin, Ca(2+) slightly stimulated calcineurin activity. Pb(2+) did not substitute for Ca(2+) in calmodulin-free activation; in fact, high concentrations of Pb(2+) inhibited Ca(2+)-mediated activation. We tentatively conclude that low concentrations of free Pb(2+) activate calcineurin by activating calmodulin. Higher concentrations reduce calcineurin activity, perhaps by binding to the B subunit.
Cyclin dependent kinase 4 (cdk4) activity is controlled by the binding of regulatory subunits and inhibitory factors, as well as tyrosine and serine/threonine phosphorylation. More recently the influence of calcium levels have been demonstrated. Using transient transfections in Jurkat cells, we observed specific binding between cdk4 and the calcium and calmodulin activated serine/threonine phosphatase, calcineurin. Furthermore, we demonstrated that the inhibition of the phosphatase activity of calcineurin with FK506 and cyclosporin A resulted in an overall increase in cdk4 kinase activity, suggesting that the phosphatase activity of calcineurin was inhibitory to the kinase activity of cdk4. In contrast, we were not able to observe a similar effect on the kinase activity of either cdk6 or cdk2, indicating that the phosphatase activity of calcineurin was specific for cdk4. In addition, using an in vitro phosphatase assay for calcineurin, we observed that the exogenous addition of calcineurin resulted in the dephosphorylation of cdk4, an event that downregulated the kinase activity of cdk4. Calcineurin could, therefore, play an opposing role to the action of the cyclin activating kinase complex, an enzyme that upregulates the kinase activity of cdk4, an important G0/G1 checkpoint element in mammalian cells. Oncogene (2000) 19, 2820 - 2827
We demonstrate that the differential effects Cbl and oncogenic 70Z/3 Cbl have on Ca(2+)/Ras-sensitive NF-AT reporters is partially due to their opposing ability to regulate phospholipase Cgamma1 (PLCgamma1) activation as demonstrated by analysis of the activation of an NF-AT reporter construct and PLCgamma1-mediated inositol phospholipid (PI) hydrolysis. Cbl over-expression resulted in reduced T cell receptor-induced PI hydrolysis, in the absence of any effect on PLCgamma1 tyrosine phosphorylation. In contrast, expression of 70Z/3 Cbl led to an increase in basal and OKT3-induced PLCgamma1 phosphorylation and PI hydrolysis. These data indicate that Cbl and 70Z/3 Cbl differentially regulate PLCgamma1 phosphorylation and activation. The implications of these data on the mechanism of Cbl-mediated signaling regulation are discussed.