Sci. Signal., 4 December 2012
Distinguishing Between PI3Kβ ActivatorsThe 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 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-binding site of p110β and developed an inhibitor peptide that blocked Gβ-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-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 Is Required for Cellular Transformation and Invasiveness. Sci. Signal. 5, ra89 (2012).
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