Wee1-like protein kinase 2 (WEE2)

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific serine/threonine and tyrosine kinase that plays a dual regulatory role in female meiosis and fertilization. WEE2 is critical for maintaining the arrest of mammalian oocytes at prophase I prior to ovulation and for enabling the resumption and completion of meiosis at fertilization by phosphorylating and thereby inhibiting cyclin-dependent kinase 1 (CDK1). Mutations in the WEE2 gene are linked to total fertilization failure and female infertility in humans. WEE2 serves as a promising non-hormonal contraceptive target because it is oocyte-restricted and not expressed in somatic tissues, minimizing systemic effects. Experimental WEE2 inhibitors prevent oocyte activation and fertilization by blocking the exit from metaphase II arrest. However, rodent models suggest WEE2 is partially dispensable for fertility due to compensation by other family members, raising translatability issues. Current inhibitor development focuses on molecules selective for WEE2 over WEE1, to avoid off-target mitotic disruption in somatic cells[1][2][3].

Other names

Wee1-like protein kinase 2WEE2WEE1BFLJ16107Wee1B kinaseOOMD5OZEMA5WEE1 homolog 2wee1-like protein kinase 1B

Inhibition of WEE2 prevents its phosphorylation of CDK1, maintaining meiotic arrest or blocking exit from metaphase II, thereby blocking fertilization[1]. Non-selective WEE inhibitors (e.g., MK-1775) inhibit both WEE1 and WEE2, but only WEE2-selective inhibition is proposed for non-hormonal contraception[1].