title: La3+ stimulate the activity of calcineurin in two different ways.
abstract: It is well known that the activity of calcineurin (CaN) could be modulated by several transitional metal ions. In the present work, the effects of a calcium analog, lanthanum ion (La(3+)), on the activity of CaN were studied. It was found that La(3+) exerted multiple effects on CaN activity. La(3+) could stimulate CaN in the absence of calmodulin (CaM); whereas at low concentrations of La(3+), there was a slight inhibition of activation of CaN in the presence of CaM. Competitive experiments and limited trypsin proteolysis confirmed that La(3+) did not act on the catalytic core of CaN, but exerted its effect through direct action on the CaN regulatory domain similar to Mg(2+). In activity titration and spot blotting studies, La(3+)-containing CaM complexes were less effective in stimulating CaN than Ca(2+) or Mn(2+)-containing CaM; however, the binding affinity of these metal-CaM complexes to CaN was similar. These effects of La(3+) on CaN activity are unique among metal ions and may provide clues to understand the biological effects of La(3+).
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100083, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Yang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
mesh_terms: D019703:Calcineurin / Q000737:chemistry* / Q000187:drug effects*; D002147:Calmodulin / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology*
chemical_list: D002147:Calmodulin; D002412:Cations; D007811:Lanthanum; D019703:Calcineurin