PTEN Pathway

PTEN Pathway

PTEN is a tumor suppressor gene that is able to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate (PI-3,4,5-P₃), the product of phosphatidyl inositol 3-kinase (PIK). Many of the mutations that have arisen in cancer cells have been mapped to the phosphatase catalytic domain of PTEN. Data suggests that the phosphatase activity of PTEN is essential for its function as a tumor suppressor. The activation of Akt/PKB is regulated by the phosphorylation of Akt on Thr³⁰⁸ and Ser⁴⁷³ by phosphoinositide-dependent kinase (PDK) and integrin-linked kinase (ILK), respectively. Inactivation of PTEN allows constitutive and unregulated activation of the Akt/PKB signaling pathway. In addition to regulating the Akt/PKB signaling pathway, PTEN also inhibits growth factor (GF)-induced Shc phosphorylation and suppresses the MAP kinase signaling pathway. PTEN interacts directly with FAK and is able to dephosphorylate activated FAK. PTEN-induced down-regulation of p130^CAS through FAK results in inhibition of cell migration and spreading.

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References:

Simpson, L., and Parsons, R., PTEN: life as a tumor suppressor. Exp. Cell Res., 264, 29-41 (2001).

Besson, A., et al., PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis. Eur. J. Biochem., 263, 605-611 (1999).