The Tumor Suppressor PTEN Is Phosphorylated by the Protein Kinase CK2 at Its C Terminus: IMPLICATIONS FOR PTEN STABILITY TO PROTEASOME-MEDIATED DEGRADATION
The tumor suppressor phosphatase PTEN regulates cell migration, growth, and survival by dephosphorylating phosphatidylinositol second messengers and signaling phosphoproteins. PTEN possesses a C-terminal noncatalytic regulatory domain that contains multiple putative phosphorylation sites, which could play an important role in the control of its biological activity. The protein kinase CK2 phosphorylated, in a constitutive manner, a cluster of Ser/Thr residues located at the PTEN C terminus. PTEN-phosphorylated defective mutants showed decreased stability in comparison with wild type PTEN and were more rapidly degraded by the proteasome. Inhibition of PTEN phosphorylation by the CK2 inhibitor 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole also diminished the PTEN protein content. Our results support the notion that proper phosphorylation of PTEN by CK2 is important for PTEN protein stability to proteasome-mediated degradation.
Torres Ibáñez, José Manuel Pulido Murillo, Rafael 2001 The Tumor Suppressor PTEN Is Phosphorylated by the Protein Kinase CK2 at Its C Terminus: IMPLICATIONS FOR PTEN STABILITY TO PROTEASOME-MEDIATED DEGRADATION Journal of Biological Chemistry 276 2 993 998