Phosphatidylinositol 4-phosphate increases the rate of dephosphorylation of the phosphorylated Ca(2+)-ATPase.

Incubation of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum with ATP in the absence of Ca2+ leads to phosphorylation of phosphatidylinositol (PtdIns) to phosphatidylinositol 4-phosphate (PtdIns-4P) and to a doubling of ATPase activity. Similarly, reconstitution of the ATPase with mixtures of dioleoylphosphatidylcholine and PtdIns-4P also led to a doubling of activity; ATPase activity increased with increasing PtdIns-4P content, up to 10% beyond which no further increase was observed. Reconstitution with PtdIns had a much smaller effect on activity. Changes in the Ca2+ affinity of the ATPase following incubation with ATP or reconstitution with PtdIns-4P were small. The rates of phosphorylation of the ATPase by ATP and of the Ca2+ transport step were unaffected, but the rate of dephosphorylation of the phosphorylated ATPase increased by a factor of 2 either following incubation with ATP or following reconstitution with PtdIns-4P. Activation of the ATPase led to a decrease in the level of phosphorylation of the ATPase by Pi corresponding to a 10-fold decrease in the equilibrium constant E2PMg/E2PiMg.