Direct identification of PTEN phosphorylation sites.
FEBS Lett
; 528(1-3): 145-53, 2002 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-12297295
ABSTRACT
The PTEN tumor suppressor gene encodes a phosphatidylinositol 3'-phosphatase that is inactivated in a high percentage of human tumors, particularly glioblastoma, melanoma, and prostate and endometrial carcinoma. Previous studies showed that PTEN is a seryl phosphoprotein and a substrate of protein kinase CK2 (CK2). However, the sites in PTEN that are phosphorylated in vivo have not been identified directly, nor has the effect of phosphorylation on PTEN catalytic activity been reported. We used mass spectrometric methods to identify Ser(370) and Ser(385) as in vivo phosphorylation sites of PTEN. These sites also are phosphorylated by CK2 in vitro, and phosphorylation inhibits PTEN activity towards its substrate, PIP3. We also identify a novel in vivo phosphorylation site, Thr(366). Following transient over-expression, a fraction of CK2 and PTEN co-immunoprecipitate. Moreover, pharmacological inhibition of CK2 activity leads to decreased Akt activation in PTEN+/+ but not PTEN-/- fibroblasts. Our results contrast with previous assignments of PTEN phosphorylation sites based solely on mutagenesis approaches, suggest that CK2 is a physiologically relevant PTEN kinase, and raise the possibility that CK2-mediated inhibition of PTEN plays a role in oncogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Monoéster Fosfórico Hidrolases
/
Proteínas Supressoras de Tumor
Tipo de estudo:
Diagnostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article