Wee1-like protein kinase 2 (WEE2) (WEE2)

Wee1-like protein kinase 2 (WEE2), also known as WEE1B, is an oocyte-specific protein tyrosine kinase that serves as a master regulator of the meiotic cell cycle in females [UniProt, NIH]. It functions by phosphorylating the cyclin-dependent kinase 1 (CDK1) at the Tyr-15 residue, which inhibits the CDK1/cyclin B complex, also known as the maturation-promoting factor [UniProt, PubMed]. This inhibitory activity is crucial for maintaining oocytes in meiotic arrest at the germinal vesicle stage and for orchestrating the exit from metaphase II during fertilization [NIH, Biology of Reproduction]. Genetic mutations in WEE2 are clinically linked to female infertility, specifically characterized by oocyte maturation arrest and total fertilization failure [GeneCards, PubMed]. Because of its highly restricted expression in the female germline and its essential role in reproduction, WEE2 is a promising target for the development of non-hormonal contraceptives [NIH, Journal of Biological Chemistry]. Therapeutic strategies involve the identification of selective small-molecule inhibitors, such as GPHR-00336382, that can disrupt WEE2 function without cross-reacting with the somatic homolog WEE1, thereby avoiding systemic toxicity [NIH, Dark Kinome].

Other names

WEE2 oocyte meiosis inhibiting kinaseWEE1BWee1-like protein kinase 1BWEE1 homolog 2Oocyte maturation defect 5Female infertility due to oocyte meiotic arrest 5FLJ16107

Inhibition of WEE2-mediated phosphorylation of CDK1 at Tyr-15, thereby modulating meiotic arrest and fertilization.