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Model for the role of WDFY2 and BACE1 in IR internalization into endosomes in hepatocytes. After insulin stimulation, the IR internalizes into endosomes. WDFY2 interacts with the IR to localize it to endosomes such that downstream IRS1/2 and AKT2 can be recruited to the endosomal IR. BACE1, located at the early endosomes, cleaves the IR-ECD and decreases the number of mature IRs. WDFY2, WD Repeat and FYVE domain containing 2; BACE1, β-site amyloid precursor protein cleaving enzyme 1.
