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. Author manuscript; available in PMC: 2016 Jan 23.
Published in final edited form as: Oncogene. 2014 Oct 6;34(30):3968–3976. doi: 10.1038/onc.2014.328

Figure 6. Model of PI3K-dependent P-REX1 positive feedback to activate Rac, IGF-1R/InsR, PI3K/AKT, and MEK/ERK signaling.

Figure 6

Growth factor receptor tyrosine kinases (RTKs) and G-protein coupled receptors (GPCRs) activate PI3K, which produces PIP3. P-REX1 is recruited to the membrane via PH domain binding to PIP3. Activation of GPCRs induces dissociation of Gβγ subunits, which bind the P-REX1 DH domain to promote its GEF activity and Rac activation. Rac activates PI3K/p110β to increase PIP3 production, stimulates Raf/MEK signaling via Pak, interacts with p-ERK, and promotes actin cytoskeleton remodeling. P-REX1 also promotes PI3K-independent activation of IGF-1R/InsR, which can lead to further activation of PI3K and MEK signaling.