Protein phosphatase type 2C active at physiological Mg2+: stimulation by unsaturated fatty acids.
Type 2C serine/threonine protein phosphatases (PP2C) so far require unphysiologically large amounts of Mg2+ ions for activity. Activators and inhibitors are not available, targeting subunits unknown. Studying the regulation of PP2C isozymes in bovine retinae, we found that the activity of PP2C increased specifically by the addition of mono- and polyunsaturated fatty acids. Activation was most pronounced at low Mg2+ levels (10-fold stimulation of PP2Calpha by 0.5 mM arachidonic acid at 0.7 mM Mg2+). Sensitivity of PP2Cbeta was 30-50% less, revealing for the first time enzymatic differences among the PP2C isozymes. Combining unsaturated fatty acids with physiological Mg2+ concentrations resulted in PP2C activity that by far exceeded the dephosphorylation rates obtained otherwise. This suggests that PP2C activity has been severely underestimated in the past. In the presence of fatty acids, Ca2+ ions became inhibitory in the micromolar range. We conclude that unsaturated fatty acids may play a role in the regulation of PP2C activity.
Klumpp
S
S
Universität, Institut für Pharmazeutische Chemie, Abteilung Biochemie, Marburg, Germany. klumpp@mailer.uni-marburg.de
Selke
D
D
Hermesmeier
J
J
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000378:metabolism; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D011994:Recombinant Proteins; D012160:Retina; D029701:Saccharomyces cerevisiae Proteins
D002413:Cations, Divalent; D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D008274:Magnesium; D002118:Calcium