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Sci. STKE, 21 November 2006
Vol. 2006, Issue 362, p. pe49
[DOI: 10.1126/stke.3622006pe49]

PERSPECTIVES

PTEN Regulation, a Novel Function for the p85 Subunit of Phosphoinositide 3-Kinase

Domingo F. Barber1, Maria Alvarado-Kristensson1, Ana González-García1, Rafael Pulido2, and Ana C. Carrera1*

1Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superiod de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
2Centro de Investigación Príncipe Felipe, Avda. Autopista del Saler 16, Valencia E-46013, Spain.

Abstract: Timely regulation of phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] abundance in cells is essential for the control of cellular homeostasis. The concentrations of these lipids are low in quiescent cells but rapidly and transiently increase following growth factor receptor (GFR) stimulation, which triggers cellular metabolic changes, proliferation, survival, and motility. Class IA phosphatidylinositol 3-kinase (PI3K), which is composed of a p85 (regulatory) and p110 (catalytic) subunits, is the enzyme generating PI(3,4)P2 and PI(3,4,5)P3 following GFR stimulation. Although the steps in GFR-induced activation of PI3K , are relatively well known, the mechanisms for subsequent 3-polyphospho-PI down-regulation are less understood. Examination of frequent genetic alterations in human cancer showed that PTEN (phosphatase with tensin homology on chromosome 10) is the major enzyme that decreases PI(3,4)P2 and PI(3,4,5)P3 cell content. Nonetheless, interpretation of the complexity of PTEN regulation remains a matter of debate. The recent description of diminished PTEN activity in liver-conditional knockout mice lacking the p85{alpha} PI3K regulatory subunit reveals a previously unknown p85{alpha}-dependent negative-feedback pathway that controls PI(3,4)P2 and PI(3,4,5)P3 half-life by regulating PTEN.

*Corresponding author. E-mail: acarrera{at}cnb.uam.es

Citation: D. F. Barber, M. Alvarado-Kristensson, A. González-García, R. Pulido, A. C. Carrera, PTEN Regulation, a Novel Function for the p85 Subunit of Phosphoinositide 3-Kinase. Sci. STKE 2006, pe49 (2006).

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