The Tumor Suppressor PTEN Is Phosphorylated by the Protein Kinase CK2 at Its C Terminus
By Josema Torres, R. Pulido. Journal of Biological Chemistry, 2001
662 citations recorded by the source corpus.
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.
Subfields: Genetics, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7d875104c0d0daf8cbf4ea420d3a1fb7c3d22343
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Citations in the corpus
- Modulation of mammalian life span by the short isoform of p53. (2004, background): “In addition to this apparent protein instability, phosphorylation at the site modified by casein kinase II (CKII; Torres and Pulido 2001; Vazquez et al. 2001; Miller et al. 2002) is dramatically increased (Fig.”
- Tenets of PTEN tumor suppression. (2008, background): “(B) PTEN interacting proteins include the kinases CK2, GSK3β (which can phosphorylate PTEN at the C terminus), and ROCK (which targets the C2 domain).”
- NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. (2007, positive): “PTEN has been shown to be phosphorylated in cells, and the phosphorylation appears to affect PTEN function (Adey et al., 2000; Leslie and Downes, 2004; Torres and Pulido, 2001; Vazquez et al., 2000).”
- The PTEN–PI3K pathway: of feedbacks and cross-talks (2008, background): “On the other hand, ubiquitinylation-dependent proteasomal degradation of PTEN reduces its levels (Torres and Pulido, 2001; Wu et al., 2003; Wang et al., 2007).”