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. 2022 Jul 14;23(14):7793. doi: 10.3390/ijms23147793

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Activated IR endocytosis, regulated by the IRS and MAD2. The IRS proteins directly bind to the IR-JM domain and interact with AP2; p31^comet suppresses the interaction of BUBR1-CDC20-AP2 and IR-bound MAD2, thus interfering with IR endocytosis in the basal state. The connection of BUBR1-CDC20-AP2 and IR-MAD2 causes IR endocytosis. SHP2, Src homology phosphatase 2; ERK, extracellular-signal-regulated kinase; AP2, assembly polypeptide 2; Y612/Y632/Y662, IR tyrosine phosphorylates the YXXΦ motifs on the IRS1. S616/S636/S666, activate ERK phosphorylates on the IRS1.