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. 2013 Jun 7;45(6):e26. doi: 10.1038/emm.2013.49

Figure 3.

Figure 3

Involvement of GIPC1 in endosomal signaling. (a) GIPC1-mediated early endosomal signaling from receptor tyrosine kinases (RTKs). IGF1R and NTRK1 are GIPC1-interacting RTKs, while APPL1 is a scaffold protein that interacts with GIPC1, RTK, Rab5, PI3K and AKT. GIPC1–RTK and GIPC1–APPL1 complexes are assembled on early endosomes through GIPC1 dimerization or RTK–APPL1 interaction. Internalized RTKs clustered with APPL1 preferentially activate the PI3K–AKT signaling cascade. (b) GIPC1-mediated early endosomal signaling from G protein-coupled receptors (GPCRs). Adrenergic receptor β1 (ADRB1) and dopamine receptor D2 (DRD2) are GIPC1-interacting GPCRs. ADRB1 transduces signals to Gαs and Gαi, while DRD2 transduces signals to Gαi. RGS19 is a GTPase activating protein that can inactivate Gαi. GIPC1–GPCR and GIPC1–RGS19 complexes are assembled on early endosomea through GIPC1 dimerization. RGS19 clustered with internalized GPCRs attenuates Gαi signaling.