Regulation of mouse gamete interaction by a sperm tyrosine kinase.
A 95-kDa mouse sperm protein has been previously identified as a putative receptor involved in the sperm-egg interactions that lead to fertilization. The ligand for this receptor is the zona pellucida glycoprotein ZP3. This constituent of the oocyte-specific extracellular matrix mediates not only sperm binding to the zona but also triggers acrosomal exocytosis. The latter, also termed the acrosome reaction, is a key regulatory event upon which fertilization is absolutely dependent. Previously, we showed that the 95-kDa protein that binds ZP3 is a substrate for tyrosine kinase, and its phosphotyrosine content increases after sperm-zona pellucida binding. Here, we show the presence of protein tyrosine kinase activity in sperm plasma membranes and in electroeluted 95-kDa protein. The tyrosine kinase activity of the isolated protein is stimulated by solubilized zona pellucida and inhibited by tyrphostin RG-50864, a membrane-permeable tyrosine kinase inhibitor. Furthermore, tyrphostin inhibits zona-triggered acrosomal exocytosis in a dose-dependent manner. These findings indicate that the 95-kDa protein participates in a critical regulatory event of gamete interaction; moreover, our experiments suggest that sperm protein tyrosine kinase may be an excellent target for the control of fertility.
D000177:Acrosome / Q000502:physiology; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004527:Egg Proteins; D005260:Female; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009570:Nitriles / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D013084:Sperm-Ovum Interactions; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020032:Tyrphostins; D000072216:Zona Pellucida Glycoproteins
D002396:Catechols; D004527:Egg Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D009570:Nitriles; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D020032:Tyrphostins; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; C035027:egg surface sperm receptor; C060152:tyrphostin 47; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases