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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-6-21
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
286-91
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12077256-Alanine,
pubmed-meshheading:12077256-Amino Acid Sequence,
pubmed-meshheading:12077256-Amino Acid Substitution,
pubmed-meshheading:12077256-Cells, Cultured,
pubmed-meshheading:12077256-Down-Regulation,
pubmed-meshheading:12077256-Feedback,
pubmed-meshheading:12077256-Half-Life,
pubmed-meshheading:12077256-Humans,
pubmed-meshheading:12077256-Jurkat Cells,
pubmed-meshheading:12077256-Molecular Sequence Data,
pubmed-meshheading:12077256-PTEN Phosphohydrolase,
pubmed-meshheading:12077256-Phosphatidylinositol Phosphates,
pubmed-meshheading:12077256-Phosphatidylinositols,
pubmed-meshheading:12077256-Phosphoric Monoester Hydrolases,
pubmed-meshheading:12077256-Phosphorylation,
pubmed-meshheading:12077256-Serine,
pubmed-meshheading:12077256-T-Lymphocytes,
pubmed-meshheading:12077256-Tumor Suppressor Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
Negative feedback regulation of the tumor suppressor PTEN by phosphoinositide-induced serine phosphorylation.
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pubmed:affiliation |
Program of Signal Transduction, Burnham Institute, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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