Erbstatin and tyrphostins block protein-serine kinase activation and meiotic maturation of sea star oocytes.
The effects of ten putative protein-tyrosine kinase inhibitors on the activation of protein-serine kinases and germinal vesicle breakdown (GVBD) in maturing sea star oocytes were investigated. Erbstatin and tyrphostins such as AG18 and AG125 blocked 1-methyladenine-induced GVBD in sea star oocytes with IC50 values of less than 20 microM. Inhibition of the rate of GBVD was achieved even when these compounds were added up to 15 min after exposure of the oocytes to 1-methyladenine. The action of these substances on oocyte maturation was reversed by subsequent washing and culturing of the cells in natural sea water free of the inhibitors. Cell viability was maintained for at least 12 h in their presence, as assessed by Trypan blue dye exclusion. These inhibitors prevented the 1-methyladenine-induced activations of the histone H1 kinase p34cdc2, the myelin basic protein kinase p44mpk and a ribosomal S6 peptide kinase. Erbstatin, AG18 and AG125 prevented 1-methyladenine-induced tyrosine dephosphorylation of p34cdc2, and they inhibited tyrosine phosphorylation of p44mpk. These studies imply that activation of a protein-tyrosine kinase may be necessary for stimulation of p34cdc2 in maturing sea star oocytes.
Daya-Makin
M
M
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Pelech
S L
SL
Levitzki
A
A
Hudson
A T
AT
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D006873:Hydroquinones / Q000494:pharmacology*; D015151:Immunoblotting; D008540:Meiosis / Q000187:drug effects*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013215:Starfish; D014443:Tyrosine / Q000378:metabolism
D002396:Catechols; D006873:Hydroquinones; D010636:Phenols; D014443:Tyrosine; C008407:1-methyladenine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D000225:Adenine; C048212:erbstatin