Research ArticleCell Biology

G Protein–Coupled Receptor–Mediated Activation of p110β by Gβγ Is Required for Cellular Transformation and Invasiveness

Science Signaling  04 Dec 2012:
Vol. 5, Issue 253, pp. ra89
DOI: 10.1126/scisignal.2003264

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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 Gβγ 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 Gβγ-binding site of p110β and developed an inhibitor peptide that blocked Gβγ-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 Gβγ-mediated activation of p110β may provide an effective therapy in the treatment of certain cancers.