J Immunol. 2002 Jul 1;169(1):286-91.

Negative feedback regulation of the tumor suppressor PTEN by phosphoinositide-induced serine phosphorylation.

Birle D, Bottini N, Williams S, Huynh H, deBelle I, Adamson E, Mustelin T.

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Program of Signal Transduction, Burnham Institute, La Jolla, CA 92037, USA.

Abstract

The PTEN tumor suppressor phosphatase directly counteracts the multiple functions of phosphatidylinositol 3-kinase by removing phosphate from the D3 position of inositol phospholipids. Like many lymphomas and leukemias, the Jurkat T cell line lacks PTEN protein due to frame-shift mutations in both PTEN alleles and therefore survives in long-term cell culture. We report that PTEN reintroduced into Jurkat was highly phosphorylated on serines 380 and 385 in its C terminus, particularly the former site. Phosphate was also detected at Ser(380) in PTEN in untransformed human T cells. Treatments that reduced the levels of D3-phospholipids in the cells resulted in reduced phosphorylation and accelerated degradation of PTEN. In contrast, expression of inactive PTEN-C124G or coexpression of a constitutively active protein kinase B led to increased phosphorylation and slower degradation of PTEN. These results suggest that PTEN normally is subjected to a feedback mechanism of regulation aimed at maintaining homeostatic levels of D3-phosphoinositides, which are crucial for T cell survival and activation.

PMID:: 12077256; [PubMed - indexed for MEDLINE]

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