INTERACTION OF A TYROSINE KINASE FROM HUMAN SPERM WITH THE ZONA-PELLUCIDA AT FERTILIZATION

A 95-kilodalton mouse sperm protein with characteristics of a protein tyrosine kinase has been identified as a receptor for ZP3, a glycoprot ein in the egg's extracellular matrix. The structure of the human homo log was determined by screening an expression library from human testi s; a testis-specific complementary DNA was isolated that encodes a pro tein similar to receptor tyrosine kinases and appears to be expressed only in testicular germ cells. Antibodies against a synthetic peptide from the intracellular domain recognized a 95-kilodalton human sperm p rotein that contains phosphotyrosine; human ZP3 stimulates the kinase activity of this sperm protein. Synthetic peptides corresponding to re gions of the predicted extracellular domain inhibited sperm binding to human zona pellucida. Availability of the primary sequence of a recep tor for ZP3 provides a rational starting point for sperm-targeted cont raceptive development.