Disruption of microtubules in living cells by tyrphostin AG-1714.
Tyrphostin AG-1714 and several related molecules with the general structure of nitro-benzene malononitrile (BMN) disrupt microtubules in a large variety of cultured cells. This process can be inhibited by the stabilization of microtubules with taxol or by pretreatment of the cells with pervanadate, which inhibits tyrosine phosphatases and increases the overall levels of phosphotyrosine in cells. Unlike other microtubule-disrupting drugs such as nocodazole or colchicine, tyrphostin AG-1714 does not interfere with microtubule polymerization or stability in vitro, suggesting that the effect of this tyrphostin on microtubules is indirect. These results imply an involvement of protein tyrosine phosphorylation in the regulation of overall microtubule dynamics. Tyrphostins of AG-1714 type could thus be powerful tools for the identification of such microtubule regulatory pathways.
Volberg
T
T
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Bershadsky
A D
AD
Elbaum
M
M
Gazit
A
A
Levitzki
A
A
Geiger
B
B
D000818:Animals; D002460:Cell Line; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine; D020032:Tyrphostins / Q000633:toxicity*; D014638:Vanadates / Q000494:pharmacology
C112766:4-nitrobenzylidene malononitrile; D004791:Enzyme Inhibitors; D020032:Tyrphostins; C076715:pervanadate; D019000:Phosphotyrosine; D014638:Vanadates; D017239:Paclitaxel