Co-existence of high levels of the PTEN protein with enhanced Akt activation in renal cell carcinoma

Recruiting Akt to the membrane-bound phosphatidylinositol (3,4,5) trisphosphate (PIP3) is required for Akt activation. While PI3 kinase (PI3K) produces PIP3, PTEN dephosphorylates the 3-position phosphate from PIP3, thereby directly inhibiting Akt activation. PTEN is the dominant PIP3 phosphatase, as knockdown of PTEN results in increases in Akt activation in mice. The PTEN tumor suppressor gene is frequently mutated in a variety of human …