Inhibition of phosphatidylinositol-4-phosphate kinase by its product phosphatidylinositol-4,5-bisphosphate

Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP 2) is enzymatically produced when high speed supernatant fraction from bovine retina is incubated with [γ- 32P]ATP and phosphatidylinositol 4-phosphate (PIP) as substrates. Exogenously added PIP 2 inhibits PIP kinase activity 50% at equimolar concentrations of product and substrate. Ca 2+-dependent phosphodiesteratic activity, resulting in the loss of PIP 2 and PIP and concommitant increase in myo -inositol 1,4,5-trisphosphate and myo -inositol 1,4-bisphosphate, was observed when soluble retinal fractions were incubated with heat-inactivated 32P-prelabeled guinea pig nerve ending membranes as substrate. It is suggested that polyphosphoinositides are under stringent and complex control and that upon receptor activation-mediated stimulation of phosphodiesteratic degradation release of the feedback inhibition shown here may occur and result in the synthesis and replenishment of PIP 2.