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 glycoprotein in the egg's extracellular matrix. The structure of the human homolog was determined by screening an expression library from human testis; a testis-specific complementary DNA was isolated that encodes a protein 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 protein that contains phosphotyrosine; human ZP3 stimulates the kinase activity of this sperm protein. Synthetic peptides corresponding to regions of the predicted extracellular domain inhibited sperm binding to human zona pellucida. Availability of the primary sequence of a receptor for ZP3 provides a rational starting point for sperm-targeted contraceptive development.