Figure 1.

Schematic of the PTEN protein. (A) PTEN contains five functional domains: two key domains that are required for its tumor-suppressor function: the phosphatase (catalytic) domain (amino acids 14–189), with an active site included within the residues 123 and 130 (black), and the C2 (lipid-membrane-binding) domain (amino acids 190–350) (red); two binding domains that are the N-terminal PIP2-binding domain PBD (amino acids 1–14) and C-terminal PDZ-binding domain (grey; amino acids 401–403), which binds proteins containing PDZ domains; the carboxy-terminal region (amino acids 351–400), which contains PEST sequences and contributes to PTEN stability and activity, and is less well defined in the tumor-suppressor functions of PTEN. Wild-type PTEN with both lipid- and protein-phosphatase activity inhibits the cell cycle, AKT activity, and cell migration. The mutation at C124S (∆LP) inactivates both PTEN lipid and protein phosphatase, which provokes the loss of the inhibition of cell-cycle arrest and AKT and cell migration. The G129E (∆L) mutant loses only its lipid-phosphatase activity and can still inhibit cell migration. The mutation of Y138L is deficient in its protein phosphatase, which may lose the capacity to inhibit cell migration. (B) Three PTEN alternative translational isoforms, PTENα, PTENβ, and PTENε, which are produced from the same mRNA as canonical PTEN and are generated due to non-AUG translational initiation. Each has a longer N-terminal extension than the canonical PTEN protein.