PTEN at a glance.

Since its discovery in 1997 (Li and Sun, 1997; Li et al., 1997; Steck et al., 1997), the phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] phosphatase and tensin homolog (PTEN) has been established as one of the most frequently mutated tumor suppressor genes in human cancer. PTEN is a phosphatase that catalyzes the conversion of the lipid second messenger PtdIns (3,4,5)P3 to phosphatidylinositol (4,5)bisphosphate [PtdIns(4,5)P2] (Maehama and Dixon, 1998). As such, PTEN functions as a main regulator of the cellular PtdIns(3,4,5)P3 concentration to antagonize the signaling cascades downstream of receptor tyrosine kinases (RTKs) and phosphatidylinositol-3-kinase (PI3K). Interestingly, PTEN might also possess protein phosphatase activity, and several potential protein substrates have been reported (Gu et al., 1999; Mahimainathan and Choudhury, 2004; Raftopoulou et al., 2004; Tamura et al., 1998). PTEN contains multiple domains, including an N-terminal phosphatase domain, a central C2 domain and a Cterminal tail. The phosphatase and C2 domains form a minimal enzymatic unit that is sufficient for metabolizing PtdIns(3,4,5)P3. The C-terminal tail is a long flexible fragment that is mainly involved in PTEN regulation. Despite having initially been discovered as a tumor suppressor, PTEN has attracted great interest from various research fields because of its diverse physiological functions. The functional diversity of PTEN demands a collection of delicate regulatory mechanisms, including transcriptional and posttranslational regulation in a tissueand context-dependent manner. This Cell Science at a Glance article summarizes the diversity of PTEN functions, and the mechanisms that underlie the regulation of PTEN expression, its enzymatic activity and subcellular localization.