The tyrosine kinase FER is responsible for the capacitation-associated increase in tyrosine phosphorylation in murine sperm.

TitleThe tyrosine kinase FER is responsible for the capacitation-associated increase in tyrosine phosphorylation in murine sperm.
Publication TypeJournal Article
Year of Publication2016
AuthorsAlvau A, Battistone MA, Gervasi MG, Navarrete FA, Xu X, Sánchez-Cárdenas C, De la Vega-Beltran JL, Da Ros VG, Greer P, Darszon A, Krapf D, Salicioni AM, Cuasnicu P, Visconti PE
JournalDevelopment
Date Published2016 May 25
ISSN1477-9129
Abstract

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.

DOI10.1242/dev.136499
Alternate JournalDevelopment
PubMed ID27226326