Document Detail


The phosphatidylinositol phosphatase PTEN is under control of costimulation and regulates proliferation in human T cells.
MedLine Citation:
PMID:  11932928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The phosphatidylinositol phosphatase gene PTEN is a dual specific phosphatase acting on phospho amino acids but also on three phosphorylated inositol phospholipids. Present results demonstrate that PTEN is inducible by costimulatory signals in human CD4(+) T cells. PTEN expression was up-regulated on RNA and protein level in freshly isolated human CD4(+) T cells following stimulation with CD28 or CD2. In contrast, PTEN expression was high but remained CD28 and CD2 unresponsive in lymphoma cells. Intracellular staining revealed PTEN expression in CD4(+) T cell populations stimulated with anti-CD28 or anti-CD28 / anti-CD3. Stimulation with anti-CD3 alone did not induce PTEN expression. Inhibition of PTEN expression by antisense oligonucleotides in CD4(+) T cells stimulated with non-mitogenic anti-CD28 resulted in massively increased proliferation, which was sensitive to the phosphatidylinositol 3-kinase (PI3 K) inhibitor wortmannin. Although CD28 and CD2 induce PI3 K signal transduction, wortmannin did not block PTEN up-regulation by CD28 or CD2 indicating that PTEN gene expression is PI3 K independent. These results demonstrate that PTEN negatively controls costimulatory signals by antagonizing PI3 K activity in the absence of TCR engagement.
Authors:
Carsten B Schmidt-Weber; Jan G Wohlfahrt; Cezmi A Akdis; Kurt Blaser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  32     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-04     Completed Date:  2002-05-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1196-204     Citation Subset:  IM    
Affiliation:
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. csweber@siaf.unizh.ch
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  physiology
Adult
Androstadienes / pharmacology
Antigens, CD2 / physiology*
Antigens, CD28 / physiology*
CD4-Positive T-Lymphocytes / cytology,  enzymology*
Cell Cycle
Cell Division / physiology
Cells, Cultured / cytology,  enzymology
Enzyme Activation
Enzyme Induction
Enzyme Inhibitors / pharmacology
Humans
Lymphocyte Activation
Lymphoma, T-Cell / genetics,  metabolism,  pathology
Oligodeoxyribonucleotides, Antisense / pharmacology
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases / biosynthesis,  genetics,  physiology*
RNA, Messenger / biosynthesis
Receptors, Antigen, T-Cell / immunology
Signal Transduction / drug effects
Thionucleotides / pharmacology
Tumor Cells, Cultured / cytology,  enzymology
Tumor Suppressor Proteins / biosynthesis,  genetics,  physiology*
Chemical
Reg. No./Substance:
0/Androstadienes; 0/Antigens, CD2; 0/Antigens, CD28; 0/Enzyme Inhibitors; 0/Oligodeoxyribonucleotides, Antisense; 0/RNA, Messenger; 0/Receptors, Antigen, T-Cell; 0/Thionucleotides; 0/Tumor Suppressor Proteins; 19545-26-7/wortmannin; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase

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