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 upon interaction with both receptor tyrosine kinases (RTK) and G-prote ins resulting in the production of moieties involved in the inositol p hospholipid signalling pathway. As G proteins, RTK and the inositol ph ospholipids have all been implicated in the human sperm acrosome react ion, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome re action induced by both mannose-bovine serum albuinin (mannose-BSA) (10 , 50 and 100 nM) and a polyclonal antibody raised against an extracell ular region of the sperm zona receptor kinase (ZRK, at 100 nM only). W ortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI S-kinase is involved in the h uman sperm acrosome reaction. The levels of tyrosine phosphorylation o f sperm proteins as detected by Western blotting using antiphosphotyro sine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase o perates downstream of tyrosine phosphorylation in the signal transduct ion cascade which leads to the human sperm acrosome reaction.