02437nas a2200265 4500008004100000245012900041210006900170260001600239520142800255100001901683700003201702700002701734700002501761700001501786700003201801700003501833700002201868700001701890700002101907700001701928700002601945700002301971700002301994856015402017 2016 ENG d00aThe tyrosine kinase FER is responsible for the capacitation-associated increase in tyrosine phosphorylation in murine sperm.0 atyrosine kinase FER is responsible for the capacitationassociate c2016 May 253 a
Sperm capacitation is required for fertilization. At the molecular level, this process is associated with a fast activation of protein kinase A. Downstream of this event, capacitating conditions lead to an increase in tyrosine phosphorylation. The identity of the tyrosine kinase(s) mediating this process has not been conclusively demonstrated. Recent experiments using stallion and human sperm have suggested a role for PYK2 based on the use of small molecule inhibitors directed against this kinase. However, critical loss-of-function experiments have not been reported. Here, we used both pharmacological inhibitors and genetically modified mice models to investigate the identity of the tyrosine kinase(s) mediating the increase in tyrosine phosphorylation in mouse sperm. Similar to stallion and human, PF431396 blocks the capacitation-associated increase in tyrosine phosphorylation. Yet, sperm from Pyk2(-/-) mice displayed normal increase in tyrosine phosphorylation, implying that PYK2 is not responsible for this phosphorylation process. Here we show that PF431396 can also inhibit FER, a tyrosine kinase known to be present in sperm. Sperm from mice targeted with a kinase inactivating mutation in Fer failed to undergo capacitation-associated increases in tyrosine phosphorylation. While these mice are fertile, their sperm displayed a reduced ability to fertilize metaphase-II arrested eggs in vitro.
1 aAlvau, Antonio1 aBattistone, Maria, Agustina1 aGervasi, Maria, Gracia1 aNavarrete, Felipe, A1 aXu, Xinran1 aSánchez-Cárdenas, Claudia1 aDe la Vega-Beltran, Jose, Luis1 aDa Ros, Vanina, G1 aGreer, Peter1 aDarszon, Alberto1 aKrapf, Diego1 aSalicioni, Ana, Maria1 aCuasnicu, Patricia1 aVisconti, Pablo, E uhttps://www.umass.edu/veterinary-animal-sciences/research-faculty/publications/the-tyrosine-kinase-fer-is-responsible-for-the-capacitation-associated