PTEN: a newly identified regulator of neuronal differentiation.

Even though phosphorylation of phosphatidylinositols by phosphoinositide 3-kinase has an important and pervasive role in the nervous system, little is known about the phosphatases that reverse this reaction. Recently, such a phosphatase, PTEN, was cloned as a tumor suppressor for gliomas. We now know that PTEN is a tumor suppressor for many tumor types and is a phosphatidylinositol phosphatase specific for the 3-position of the inositol ring. PTEN is expressed in most, if not all, neurons and is localized in the nucleus and cytoplasm. PTEN is not evident in neural processes or synapses. PTEN is induced during neuronal differentiation and is required for survival of differentiating neuronal cells. In summary, PTEN is a regulatory molecule with multiple functions at multiple subcellular sites. Further studies are required to determine which downstream pathways are regulated by PTEN, by which mechanisms PTEN activity is regulated, which stimuli regulate PTEN activity, and why a molecule that inhibits several survival pathways is induced during neurogenesis.