. Protein kinase A (PKA) activity and Src family kinases (SFK) inhibitors effect in stallion sperm under capacitating conditions

6. VIVANI L., GRADIL C, MUTTO A AND VISCONTI P

THERIOGENOLOGY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2013

0093-691X

After ejaculation, mammalian spermatozoa must undergo a series of complex and poorly understood cellular events known as ?capacitation? in order to be able to fertilize an oocyte (Yanagimachi, 1994). Among these, biochemical changes such as an increase in tyrosine phosphorylation of some sperm proteins has been correlated with the sperm capacity to fertilize an egg and found to be regulated by a cAMP dependent pathway (Visconti et al., 1995). The influx of ions such as Ca2+ and HCO3- induce the activation of a soluble adenylyl cyclase (SACY) increasing the cAMP levels within the cell that leads to the activation of a protein kinase A (PKA), and a subsequently increase in protein tyrosine phosphorylation. This modification in sperm proteins seems to be essential for induction of a change in the motility pattern known as hyperactivation that enables the sperm to penetrate the zona pellucida of the oocyte and initiate fertilization (Asquith et al., 2004). Since PKA is a serine/threonine kinase, it is not clear how it mediates protein tyrosine phosphorylation during sperm capacitation. Based on the finding that in somatic cells PKA activates c-Src, it has been proposed that the Src family of protein kinases (SFK) are the intermediate players involved in tyrosine phosphorylation induced by PKA activity. This hypothesis is supported by the fact that c-Src which is the prototypic member of the SFK, is present in mouse sperm and its inhibition by SU6656 blocks the increase in tyrosine phosphorylation and the hyperactivated motility pattern (Baker et al; 2006). Furthermore, acrosome reaction has been inhibited in human and bull sperm with SFK inhibitors (Varano et al., 2008; Etkovitz et al., 2009).