Reining in Tumor Suppression

Science Signaling  08 Sep 2009:
Vol. 2, Issue 87, pp. ec297
DOI: 10.1126/scisignal.287ec297

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]