Inhibition of serum-induced M-phase progression by a tyrosine kinase inhibitor, erbstatin.
A tyrosine kinase inhibitor, erbstatin, increased the number of M-phase cells in exponentially growing NRK, NIH3T3, and RSV-NRK cells. In synchronized NRK cells prepared by serum starvation or hydroxyurea treatment, erbstatin also increased the number of M-phase cells in the presence of serum when added before M-phase. Erbstatin did not inhibit serum-induced DNA synthesis at all. The accumulated M-phase cells later divided even in the presence of erbstatin, indicating that the effect of erbstatin is reversible. An inactive analogue, 5'-O-methylerbstatin, did not increase the number of mitotic figures. Flow cytometric analysis indicated that erbstatin reversibly accumulated 4n DNA containing cells when added to G1/S-synchronized NRK cells. Increased cellular H1 kinase activity at M-phase is decreased after mitosis, and this decrease was inhibited by erbstatin. Thus tyrosine kinase is suggested to be involved in the progression of the M-phase.
Sugata
D
D
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Yamashita
K
K
Umezawa
K
K
D016475:3T3 Cells; D000818:Animals; D001769:Blood; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004261:DNA Replication / Q000187:drug effects; D006873:Hydroquinones / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D008940:Mitotic Index / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats
D016895:Culture Media, Serum-Free; D006873:Hydroquinones; D011505:Protein-Tyrosine Kinases; C048212:erbstatin; D006918:Hydroxyurea