EFFECTS OF PROTEIN-TYROSINE KINASE INHIBITORS ON EGG ACTIVATION AND FERTILIZATION-DEPENDENT PROTEIN-TYROSINE KINASE-ACTIVITY

Fertilization results in the activation of protein tyrosine kinases wi thin minutes of sperm-egg binding, although the role of the kinase(s) involved is not clear. In the present study, we have treated sea urchi n eggs with genistein, as well as other protein tyrosine kinase inhibi tors, and have characterized the subsequent effect on fertilization an d egg activation. Genistein treatment of sea urchin eggs inhibits the overall fertilization-dependent tyrosine kinase-activity as well as th e specific phosphorylation of a 350-kDa protein, but it did not inhibi t cAMP-dependent kinase and had little effect on protein kinase C at c oncentrations less than 100 mu M. Genistein, erbstatin, and tyrphostin B42 did not inhibit the early events of fertilization such as elevati on of the fertilization envelope; however, later events such as pronuc lear migration, DNA synthesis, and cell division were inhibited. These results suggest that protein tyrosine kinases activated following fer tilization play a role in the later events of egg activation such as t he initiation of pronuclear movement and entry into the S phase of the cell cycle. (C) 1995 Academic Press, Inc.