Signal Transduction

Adaptable Transducers

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Science  08 May 2009:
Vol. 324, Issue 5928, pp. 693
DOI: 10.1126/science.324_693b

The α subunits of heterotrimeric guanine nucleotide–binding proteins (G proteins) associate with G protein–coupled receptors (GPCRs) at the cell membrane and transduce signals that affect a range of physiological processes. Yet there have been hints that Gα subunits may have other signaling roles as well. Cao et al. found that mouse fibroblasts lacking the Gαi1 and Gαi3 proteins had impaired signaling through the epidermal growth factor receptor (EGFR), a receptor with a signaling mechanism distinct from that of GPCRs. The protein Gab1 binds to activated EGFR and links it to activation of downstream proteins. The authors show that Gαi1 is required for this association and that in cells stimulated with EGF, Gαi1 and Gαi3 are present in a complex with Gab1 and EGFR. The effects of EGF on cell survival, proliferation, and migration were all dependent on signaling through Gα proteins, suggesting that Gαi proteins might become the targets of therapies aimed at squelching cancer cells.

Sci. Signal.2, ra17 (2009).

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