Mol. Hum. Reprod. Advance Access originally published online on February 11, 2005
Molecular Human Reproduction 2005 11(3):211-221; doi:10.1093/molehr/gah154
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Various protein kinases regulate human sperm acrosome reaction and the associated phosphorylation of Tyr residues and of the Thr-Glu-Tyr motif
1Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, Universita' degli studi di Perugia, Via del Giochetto, 06123 Perugia, Italy, 2Urology Research Laboratory, Royal Victoria Hospital and Faculty of medicine, McGill University, 687 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada
3 To whom correspondence should be addressed at: Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, Sez. Biochimica Cellulare, Università degli studi di Perugia, Via del Giochetto, 06123 Perugia. Email: lavynia{at}email.it
Acrosome reaction (AR) is an exocytotic process of fundamental importance for the spermatozoon to fertilize the oocyte. The mechanisms mediating this process are only partially defined. The aim of the present study was to investigate the role of various kinases and the extracellular signal-regulated kinase (ERK) pathway in the induction of the AR and associated phosphorylation of tyrosine (Tyr) residues and of the threonine-glutamic acid-tyrosine (Thr-Glu-Tyr) motif that occurs in 80 and 105 kDa proteins (p80/p105). Human spermatozoa were capacitated and AR was induced with lysophosphatidylcholine in the presence of inhibitors of various kinases and of the ERK pathway. Phosphorylation of Tyr and of Thr-Glu-Tyr peaked 15 min after the induction of the AR. Both phosphorylations were prevented by inhibitors of protein kinase C, MEK, phosphoinositide 3-kinase and Akt but not by protein kinase A inhibitors. Phosphorylation of Thr-Glu-Tyr, but not Tyr, was decreased by inhibitors of protein tyrosine kinase and Grb2-SH2. All the inhibitors prevented lysophosphatidylcholine-induced AR, indicating the involvement of PKC, PKA, PTK, PI3K, Akt and the ERK pathway. These results show that phosphorylation of Tyr and Thr-Glu-Tyr are associated with the AR and are differently regulated by the various kinases emphasing the complexity of this process.
Key words: lysophosphatidylcholine/protein phosphorylation/signal transduction/spermatozoa/sperm function
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