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A stepwise activation model for the insulin receptor

  • 작성자

    Yunje Cho
  • 작성일자

    2023-12-21
  • 조회수

    801
Yunje Cho( yunje@postech.ac.kr )
2013-PresentStructural Biology, Cancer Biology, POSTECH Jongryeol Hong’s Chaired Professor
2004-Professorof Life Science, POSTECH
2000-2004Associate Professor, Department of Life Science, POSTECH
1995-2000Senior Scientist, Korea Institute of Science and Technology
1993-1995Post-doc, Memorial Sloan-Kettering Cancer Center
1989-1993Ph.D. Biological Sciences (Microbiology), Cornell Univ
1986-1989M.S. Biochemistry Iowa State Univ
1982-1988B.S. Seoul National Univ

A stepwise activation model for the insulin receptor

The binding of insulin to the insulin receptor (IR) triggers a cascade of receptor conformational changes and autophosphorylation, leading to the activation of metabolic and mitogenic pathways. Recent advances in the structural and functional analyses of IR have revealed the conformations of the extracellular domains of the IR in inactive and fully activated states. However, the early activation mechanisms of this receptor remain poorly understood. The structures of partially activated IR in complex with aptamers provide clues for understanding the initial activation mechanism. In this review, we discuss the structural and functional features of IR complexed with various ligands and propose a model to explain the sequential activation mechanism. Moreover, we discuss the structures of IR complexed with biased agonists that selectively activate metabolic pathways and provide insights into the design of selective agonists and their clinical implications.

Exp Mol Med 2023 Oct;55(10):2147-2161 doi: 10.1038/s12276-023-01101-1
https://pubmed.ncbi.nlm.nih.gov/37779149/