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. 2012 Dec 1;23(23):4623–4634. doi: 10.1091/mbc.E12-02-0133

FIGURE 10:

FIGURE 10:

Working model. GIV spatially regulates the trafficking and signaling of EGFR via sequential interactions with Gαi3 and Gαs. Upon EGF stimulation, GIV binds EGFR and assembles an EGFR/GIV/Gαi3 complex at the PM that activates Gαi3 (1), prolongs the association of EGFR with the PM, and enhances PM-based Akt signaling (2). On internalization EGFR traffics to APPL endosomes (3) and then to EEA1 endosomes (4), where GIV binds inactive Gαs, and promotes dissociation of EEA1 and endosome maturation to MVEs (5), which facilitates EGFR down-regulation and shuts off proliferative signaling from endosomes.