Stimulation of tubulin-dependent ATPase activity in microtubule proteins from porcine brain by vinblas tine.
Vinblastine, a plant alkaloid which inhibits tubulin polymerization, stimulated an ATPase activity in microtubules. When microtubule proteins were separated into microtubule-associated proteins (MAPs) and tubulin by phosphocellulose column chromatography, vinblastine did not stimulate an ATPase activity recovered in the MAPs fraction unless tubulin was present. Therefore, vinblastine is considered to act through its binding to the tubulin molecule on MAPs ATPase. Divalent cations that activate tubulin-dependent MAPs ATPase activity were also required for the stimulation by vinblastine. In the presence of Ca2+ and vinblastine the ATPase activity was most active and the extent of stimulation reached about 200% of the original level in the absence of vinblastine. Half-maximal stimulation was attained when the molar ratio of vinblastine to tubulin was 0.5. The concentration of tubulin for half-maximal stimulation was increased in the presence of vinblastine, while divalent cation requirements were decreased. Several factors such as KCl (100 mM), alkaline pH (pH 7.5), and low temperature (10 degrees C) were not responsible for the disappearance of the stimulation. Vincristine stimulated tubulin-dependent MAPs ATPases activity as vinblastine did, whereas the activity was scarcely affected by colchicine, podophyllotoxin, strychnine, and chlorpromazine. Actin had no effect on MAPs ATPase activity in the absence and presence of vinblastine when it was used in place of tubulin.
D000199:Actins / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008869:Microtubule-Associated Proteins; D011506:Proteins / Q000378:metabolism*; D013552:Swine; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology*
D000199:Actins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D014404:Tubulin; D004533:Egtazic Acid; D014747:Vinblastine; D004492:Edetic Acid; D000251:Adenosine Triphosphatases; D000252:Calcium-Transporting ATPases; D008274:Magnesium