In mammals, the placenta is the lifeline between a mother and her unborn offspring. In a recent "Paper of the Week" in The Journal of Biological Chemistry, researchers demonstrated that mutations in an unusual class of phosphatases disrupted development of the placenta in mice. The phosphatases were the PRL phosphatases. “Unlike most protein phosphatases that counteract the activity of protein kinases, the PRLs play a positive role in signaling,” says Zhong-Yin Zhang at the Indiana University School of Medicine. Mutations in these phosphatases have been linked to a number of different cancers, such as those that develop in the colon, pancreas, breast and lung. Despite a wealth of data obtained in cultured cells while looking at the roles for PRLs in cell growth in organs like the placenta and metastasis, their molecular mechanisms remain a mystery. So Zhang and his colleagues deleted the most ubiquitously expressed PRL family member, PRL2, in mice. They found that the deletion disrupted placental development and interfered with the growth of embryonic and adult mice. The investigators established that PRL2 promotes placental development — and potentially cancer, when it goes awry — by targeting the tumor suppressor PTEN for degradation in the proteasome. PTEN’s function is to deactivate Akt, a master kinase involved in the regulation of cell growth and survival. Therefore, when PRL2 removes PTEN from the scene, Akt springs into action and allows cells to proliferate. For this reason, Zhang says, PRL2, when mutated, qualifies as an oncogene and may be an attractive target for anticancer drug design.
Rajendrani Mukhopadhyay (firstname.lastname@example.org) is the senior science writer for ASBMB Today and the technical editor for The Journal of Biological Chemistry. Follow her on Twitter (www.twitter.com/rajmukhop).