Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 8 September 2009
Vol. 2, Issue 87, p. ec297
[DOI: 10.1126/scisignal.287ec297]

EDITORS' CHOICE

Cancer Reining in Tumor Suppression

L. Bryan Ray

Science, Science Signaling, AAAS, Washington, DC 20005, USA

Mitogenic signaling through phosphoinositide-3 kinase generates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). The tumor suppressor gene product and lipid phosphatase PTEN (phosphatase and tensin homolog on chromosome ten) opposes such mitogenic signaling by dephosphorylating PIP3. In a screen for proteins that interact with PTEN, Fine et al. identified P-REX2a, a guanine nucleotide exchange factor (GEF) for the RAC small guanosine triphosphatase. Endogenous P-REX2a and PTEN interacted in human embryonic kidney 293 cells, and P-REX2a inhibited catalytic activity of PTEN. Thus, like that of many protein phosphatases, the activity of PTEN is kept in check by an interacting protein inhibitor. P-REX2a thus provides a mechanism through which tumor cells may inactivate PTEN.

B. Fine, C. Hodakoski, S. Koujak, T. Su, L. H. Saal, M. Maurer, B. Hopkins, M. Keniry, M. L. Sulis, S. Mense, H. Hibshoosh, R. Parsons, Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Science 325, 1261–1265 (2009). [Abstract] [Full Text]

Citation: L. B. Ray, Reining in Tumor Suppression. Sci. Signal. 2, ec297 (2009).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882