The tumor suppressor PTEN regulates T cell survival and antigen receptor signaling by acting as a phosphatidylinositol 3-phosphatase.

Abstract

The tumor suppressor gene PTEN encodes a 55-kDa enzyme that hydrolyzes both protein phosphotyrosyl and 3-phosphorylated inositol phospholipids in vitro. We have found that the latter activity is physiologically relevant in intact T cells. Expression of active PTEN lead to a 50% loss of transfected cells due to increased apoptosis, which was completely prevented by coexpression of a constitutively active, membrane-bound form of protein kinase B. A mutant of PTEN selectively lacking lipid phosphatase activity, but retaining protein phosphatase activity, had no effects on cell number. Active (but not mutant) PTEN also decreased TCR-induced activation of the mitogen-activated protein kinase ERK2 (extracellular signal-related kinase 2), as seen after inhibition of phosphatidylinositol 3-kinase. Our data indicate that PTEN is a phosphatidylinositol 3-phosphatase in T cells, and we suggest that PTEN may play a role in the regulation of T cell survival and TCR signaling by directly opposing phosphatidylinositol 3-kinase.

• Authors: X Wang, A Gjörloff-Wingren, M Saxena, N Pathan, J C Reed, T Mustelin
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 4 Pg. 1934-9 (Feb 15 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10657643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD3 Complex
• Enzyme Inhibitors
• Proto-Oncogene Proteins
• Receptors, Antigen, T-Cell
• Tumor Suppressor Proteins
• Myristic Acid
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinases
• Phosphoric Monoester Hydrolases
• phosphatidylinositol-3-phosphatase
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Apoptosis (immunology)
• CD3 Complex (immunology)
• Cell Survival (immunology)
• Enzyme Activation (immunology)
• Enzyme Inhibitors (pharmacology)
• Genes, Tumor Suppressor
• Humans
• Jurkat Cells
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Myristic Acid (metabolism)
• PTEN Phosphohydrolase
• Phosphoric Monoester Hydrolases (biosynthesis, genetics, metabolism, physiology)
• Phosphorylation
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt
• Receptors, Antigen, T-Cell (antagonists & inhibitors, metabolism, physiology)
• Signal Transduction (immunology)
• T-Lymphocytes (cytology, metabolism)
• Tumor Suppressor Proteins