Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated uponinteraction with both receptor tyrosine kinases (RTK) and G- proteinsresulting in the production of moieties involved in the inositolphospholipid signalling pathway. As G proteins, RTK and the inositolphospholipids have all been implicated in the human sperm acrosomereaction, experiments were carried out to determine whether PI 3-kinase wasalso involved in this phenomenon. Wortmannin is a selective inhibitor of PI3-kinase and was shown to significantly inhibit the acrosome reactioninduced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100nM) and a polyclonal antibody raised against an extracellular region of thesperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did notinhibit the A23187- or progesterone-induced acrosome reaction. Theseresults suggest that PI 3- kinase is involved in the human sperm acrosomereaction. The levels of tyrosine phosphorylation of sperm proteins asdetected by Western blotting using antiphosphotyrosine antibodies was notaffected by wortmannin in agonist (A23187 and mannose-BSA)-stimulatedspermatozoa. This indicated that PI 3-kinase operates downstream oftyrosine phosphorylation in the signal transduction cascade which leads tothe human sperm acrosome reaction.