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.


Sci. Signal., 4 December 2012
Vol. 5, Issue 253, p. ra89
[DOI: 10.1126/scisignal.2003264]


Editor's Summary

Distinguishing Between PI3Kβ Activators
The p110β member of the class IA phosphoinositide 3-kinases (PI3Ks) is unusual in that it is activated by receptor tyrosine kinases (RTKs) and by G protein–coupled receptors (GPCRs), in the latter case through Gβ{gamma} dimers. Tumor cells deficient in the phosphatase PTEN depend on the activity of p110β for proliferation; however, it has not been possible to assess the relative contributions of RTKs and GPCRs to p110β activity in this context. Dbouk et al. identified and characterized the Gβ{gamma}-binding site of p110β and developed an inhibitor peptide that blocked Gβ{gamma}-dependent activation of p110β in vitro but left RTK-mediated activation intact. A cell-permeable version of this peptide inhibited the proliferation and invasiveness of human PTEN-deficient tumor cell lines, suggesting that specifically targeting Gβ{gamma}-mediated activation of p110β may provide an effective therapy in the treatment of certain cancers.

Citation: H. A. Dbouk, O. Vadas, A. Shymanets, J. E. Burke, R. S. Salamon, B. D. Khalil, M. O. Barrett, G. L. Waldo, C. Surve, C. Hsueh, O. Perisic, C. Harteneck, P. R. Shepherd, T. K. Harden, A. V. Smrcka, R. Taussig, A. R. Bresnick, B. Nürnberg, R. L. Williams, J. M. Backer, G Protein–Coupled Receptor–Mediated Activation of p110β by Gβ{gamma} Is Required for Cellular Transformation and Invasiveness. Sci. Signal. 5, ra89 (2012).

Read the Full Text

Classes of phosphoinositide 3-kinases at a glance.
S. Jean and A. A. Kiger (2014)
J. Cell Sci. 127, 923-928
   Abstract »    Full Text »    PDF »
Molecular determinants of PI3K{gamma}-mediated activation downstream of G-protein-coupled receptors (GPCRs).
O. Vadas, H. A. Dbouk, A. Shymanets, O. Perisic, J. E. Burke, W. F. Abi Saab, B. D. Khalil, C. Harteneck, A. R. Bresnick, B. Nurnberg, et al. (2013)
PNAS 110, 18862-18867
   Abstract »    Full Text »    PDF »
p87 and p101 Subunits Are Distinct Regulators Determining Class IB Phosphoinositide 3-Kinase (PI3K) Specificity.
A. Shymanets, Prajwal, K. Bucher, S. Beer-Hammer, C. Harteneck, and B. Nurnberg (2013)
J. Biol. Chem. 288, 31059-31068
   Abstract »    Full Text »    PDF »
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation.
T. Balla (2013)
Physiol Rev 93, 1019-1137
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

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