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