PTEN, here, there, everywhere

摘要

Loss of function of the phosphatase and tensin homolog (PTEN) tumor suppressor is frequently found in many human malignancies. PTEN antagonizes the phosphatidylinositide 3-kinase (PI3K) pathway by dephosphorylating the 3' position of phosphatidylinositol (3,4,5)-trisphosphate [Ptdlns(3,4,5)P_3] (or PIP3). PIP3 serves as a second messenger whose levels in the plasma membrane are elevated following cell stimulation with growth factors, mediated by the activity of PI3Ks. Proteins containing pleckstrin homology (PH) domains physically interact with PIP3, bringing them into close proximity with other PH domain-containing proteins and facilitating further functional interactions that serve to propagate the membranous signal.4 PTEN contains an N-terminal phosphatase domain that displays activity not only toward phosphatydilinositol, lipid substrates, but also toward proteinacious ones, although the search for physiologically relevant protein PTEN substrates continues.