• PMID: 24371141
• Gene Name: PTP4A2
• Condition: Role in spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Role in spermatogenesis

Phosphatase of regenerating liver 2 (PRL2) deficiency impairs Kit signaling and spermatogenesis

Dong Y, Zhang L, Bai Y, Zhou HM, Campbell AM, Chen H, Yong W, Zhang W, Zeng Q, Shou W, Zhang ZY.

The Phosphatase of Regenerating Liver (PRL) proteins promote cell signaling and are oncogenic when overexpressed. However, our understanding of PRL function came primarily from studies with cultured cell lines aberrantly or ectopically expressing PRLs. To define the physiological roles of the PRLs, we generated PRL2 knock-out mice to study the effects of PRL deletion in a genetically controlled, organismal model. PRL2-deficient male mice exhibit testicular hypotrophy and impaired spermatogenesis, leading to decreased reproductive capacity. Mechanistically, PRL2 deficiency results in elevated PTEN level in the testis, which attenuates the Kit-PI3K-Akt pathway, resulting in increased germ cell apoptosis. Conversely, increased PRL2 expression in GC-1 cells reduces PTEN level and promotes Akt activation. Our analyses of PRL2-deficient animals suggest that PRL2 is required for spermatogenesis during testis development. The study also reveals that PRL2 promotes Kit-mediated PI3K/Akt signaling by reducing the level of PTEN that normally antagonizes the pathway. Given the strong cancer susceptibility to subtle variations in PTEN level, the ability of PRL2 to repress PTEN expression qualifies it as an oncogene and a novel target for developing anti-cancer agents. FAU - Dong, Yuanshu AU - Dong Y AD - From the Department of Biochemistry and Molecular Biology, and. FAU - Zhang, Lujuan AU - Zhang L FAU - Bai, Yunpeng AU - Bai Y FAU - Zhou, Hong-Ming AU - Zhou HM FAU - Campbell, Amanda M AU - Campbell AM FAU - Chen, Hanying AU - Chen H FAU - Yong, Weidong AU - Yong W FAU - Zhang, Wenjun AU - Zhang W FAU - Zeng, Qi AU - Zeng Q FAU - Shou, Weinian AU - Shou W