Abstract
Intracellular levels of phosphorylation are regulated by the coordinated action of protein kinases and phosphatases. Disregulation of this balance can lead to cellular transformation. Here we review knowledge of the mechanisms of one protein phosphatase, the tumour suppressor PTEN/MMAC/TEP 1 apropos its role in tumorigenesis and signal transduction. PTEN plays an important role in the phosphatidyl-inositol-3-kinase (PI3-K) pathway by catalyzing degradation of phosphatidylinositol-(3,4,5)-triphosphate generated by PI3-K. This inhibits downstream targets mainly protein kinase B (PKB/Akt), cell survival and proliferation. PTEN contributes to cell cycle regulation by blockade of cells entering the S phase of the cell cycle, and by upregulation of p27(Kip1) which is recruited into the cyclin E/cdk2 complex. PTEN also modulates cell migration and motility by regulation of the extracellular signal-related kinase - mitogen activated protein kinase (ERK-MAPK) pathway and by dephosphorylation of focal adhesion kinase (FAK). We also emphasize the increasingly important role that PTEN has from an evolutionary point of view. A number of PTEN functions have been elucidated but more information is needed for utilization in clinical application and potential cancer therapy.
Highlights
INTRODUCTIONPTEN (phosphatase and tensine homolog deleted on chromosome ten)/MMAC (mutated in multiple advanced cancers) has been identified simultaneously by two research groups as a candidate tumour suppressor gene located at 10q231, 2
PTEN/MMAC has been identified simultaneously by two research groups as a candidate tumour suppressor gene located at 10q231, 2
PTEN participates in the regulation of normal cell growth and survival
Summary
PTEN (phosphatase and tensine homolog deleted on chromosome ten)/MMAC (mutated in multiple advanced cancers) has been identified simultaneously by two research groups as a candidate tumour suppressor gene located at 10q231, 2. Another group identified the same gene in the search for new dual-specificity phosphatases and named it TEP-1 (TGF-β regulated and epithelial cell-enriched phosphatase)[3]. It has recently been shown that an interaction of PDZ domain with MAGI-2 stabilises the PTEN protein and enhances its activity, and threonine phosphorylation of the PDZ-binding motif both inhibits and stimulates PDZ-binding[12]
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