Inhibition of phosphatidylinositol-4-phosphate kinase by its product phosphatidylinositol-4,5-bisphosphate.
Phosphatidylinositol 4,5-bisphosphate (PIP2) is enzymatically produced when high speed supernatant fraction from bovine retina is incubated with [gamma-32P]ATP and phosphatidylinositol 4-phosphate (PIP) as substrates. Exogenously added PIP2 inhibits PIP kinase activity 50% at equimolar concentrations of product and substrate. Ca2+-dependent phosphodiesteratic activity, resulting in the loss of PIP2 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 PIP2.
Van Rooijen
L A
LA
Rossowska
M
M
Bazan
N G
NG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006168:Guinea Pigs; D006358:Hot Temperature; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000494:pharmacology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D017853:Phosphotransferases (Alcohol Group Acceptor); D012160:Retina / Q000201:enzymology; D014461:Ultracentrifugation
D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D002118:Calcium