Open AccessThe antibiotic azatyrosine suppresses progesterone or [Val12]p21 Ha-ras/insulin-like growth factor I-induced germinal vesicle breakdown and tyrosine phosphorylation of Xenopus mitogen-activated protein kinase in oocytes.
Author(s) -
Michael J. Campa,
J. Fraser Glickman,
Kyohei Yamamoto,
KwenJen Chang
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.16.7654
Subject(s) - germinal vesicle , autophosphorylation , tyrosine phosphorylation , biology , growth factor , insulin like growth factor , maturation promoting factor , microinjection , microbiology and biotechnology , phosphorylation , tyrosine kinase , protein kinase a , endocrinology , oocyte , signal transduction , cyclin dependent kinase 1 , biochemistry , cell cycle , receptor , apoptosis , embryo
The antibiotic azatyrosine [DL-3-(5-hydroxy-2-pyridyl)alanine] suppressed meiotic maturation in oocytes induced by progesterone or the combination of [Val12]p21Ha-ras microinjection and insulin-like growth factor I. The suppression was dose-dependent in the range of 20-250 microM azatyrosine. In addition, azatyrosine blocked the tyrosine phosphorylation of Xp42, a member of the mitogen-activated protein kinase family, after progesterone or [Val12]p21Ha-ras/insulin-like growth factor I stimulation. Activation of maturation-promoting factor, as shown by a decrease in the tyrosine phosphorylation of the Xenopus homolog of p34cdc2, was also suppressed by azatyrosine. Azatyrosine had no effect in vivo or in vitro on the growth factor-induced autophosphorylation of the oocyte insulin-like growth factor I receptor. Azatyrosine has been shown by others [Shindo-Okada, N., Makabe, O., Nagahara, H. & Nishimura, S. (1989) Mol. Carcinog. 2, 159-167] to inhibit the growth of ras-transformed cells without affecting that of nontransformed cells. In oocytes, the antibiotic exerts an inhibitory action on both a ras-dependent and a ras-independent pathway. Lack of an effect of azatyrosine on germinal vesicle breakdown induced by the microinjection of an extract from mature oocytes, however, suggests that azatryosine is acting upstream of maturation-promoting factor activation.