[Mechanism of action of azatyrosine: recent process].
Azatyrosine is known to convert ras, raf or c-erbB-2-transformed NIH3T3 cells to a normal phenotype. We attempted to identify the signal-transduction process triggered by oncogenic c-ErbB-2 that was inhibited by azatyrosine. Azatyrosine did not suppress activation of Ras induced by introduction of c-ErbB-2. However, it inhibited increases in phosphorylation of c-Raf-1 induced by oncogenic c-ErbB-2. Furthermore, azatyrosine inhibited activation of the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element in response to stimulation by oncogenic c-ErbB-2. These results suggest that this agent acts downstream of Ras in signal transduction from oncogenic c-ErbB-2 to nuclear factors. Moreover, we found that azatyrosine was incorporated into proteins instead of tyrosine. The simultaneous presence of a high concentration of tyrosine inhibited the conversion to a normal phenotype of transformed cells by azatyrosine. These results strongly suggest that incorporation of azatyrosine into proteins might convert the transformed cells in to cells with a normal phenotype.
Monden
Y
Y
Banyu Tsukuba Research Institute.
Shindo-Okada
N
N
Nishimura
S
S
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects; D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division; D011905:Genes, ras; D006801:Humans; D051379:Mice; D011506:Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D000409:Alanine; D000903:Antibiotics, Antineoplastic; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; C011870:beta-(5-hydroxy-2-pyridyl)alanine