Micro-injection of recombinant lysyl oxidase blocks oncogenic p21-Ha-Ras and progesterone effects on Xenopus laevis oocyte maturation.
Previous evidence suggested an anti-oncogenic role for lysyl oxidase, mainly in ras-transformed cells. Here we prove that recombinant lysyl oxidase is actually able to antagonize p21-Ha-Ras-induced Xenopus laevis oocyte maturation. Lysyl oxidase was also effective on progesterone-dependent maturation, indicating a block lying downstream of Ras. Maturation induced by activated 'maturation promoting factor', normally triggered by progesterone, was also inhibited by lysyl oxidase. Finally, lysyl oxidase did not abolish p42Erk2 phosphorylation upon maturation triggering, suggesting a block downstream of Erk2. Further investigation showed that lysyl oxidase action depends on protein synthesis and is therefore probably mediated by a newly synthesized protein.
Di Donato
A
A
Department of Nephrology, Institute G. Gaslini, Genoa, Italy. a-dido@usa.net
Lacal
J C
JC
Di Duca
M
M
Giampuzzi
M
M
Ghiggeri
G
G
Gusmano
R
R
D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016200:Maturation-Promoting Factor / Q000494:pharmacology; D008845:Microinjections; D019950:Mitogen-Activated Protein Kinase 1; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development*; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D000629:Aminopropionitrile; D011374:Progesterone; D003513:Cycloheximide; D008249:Protein-Lysine 6-Oxidase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016200:Maturation-Promoting Factor; D019950:Mitogen-Activated Protein Kinase 1; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)