Stimulation of tubulin-dependent ATPase activity in microtubule proteins from porcine brain by taxol.
Taxol, an antimitotic agent that induces microtubule assembly, stimulated tubulin-dependent Mg2+-ATPase activity of microtubule-associated proteins (MAPs). A concentration-dependent increase in the rate of ATP hydrolysis was observed. Taxol acted through its binding to the tubulin molecule on MAP ATPase, and maximal stimulation, which was found at approximately equal concentrations of taxol and tubulin, reached about 140% of the original level in the absence of taxol. Taxol enhanced ATP hydrolysis by a mixture of MAPs and tubulin, and this continued at a steady linear rate even when the polymerization had approached a plateau. In the presence of taxol, a large portion of ATPase activity and protein was recovered in the pellet after centrifugation at 70,000 g for 60 min at 25 degrees C. Both colchicine and podophyllotoxin inhibited taxol-stimulated ATPase activity via the same mechanism by which they inhibited taxol-induced microtubule polymerization. The stimulation by taxol was not found in the presence of Ca2+ alone but required Mg2+. We conclude that tubulin effectively stimulates Mg2+-ATPase activity of MAPs under conditions that induce tubulin polymerization.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D008869:Microtubule-Associated Proteins; D017239:Paclitaxel; D011034:Podophyllotoxin / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D013552:Swine; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
D000470:Alkaloids; D008869:Microtubule-Associated Proteins; D011506:Proteins; D014404:Tubulin; D014747:Vinblastine; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D011034:Podophyllotoxin; D017239:Paclitaxel; D003078:Colchicine; D002118:Calcium