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Molecular Properties of Insulin/IGF-1 Hybrid Receptors 4th International Symposium on Insulin, IGFs and Their Receptors

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Current Directions in Insulin-Like Growth Factor Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 343))

Abstract

Insulin and IGF-1 are two highly related growth factors which mediate pleiotropic cellular responses1–3. These hormones regulate their specific actions via binding to specific high affinity receptors on the plasma membrane of target cells. Similar to these growth factors, the receptors for insulin and IGF-1 share a high degree of structural and functional properties4–7. Both these receptors are classified as Type I receptors being composed of two a subunits and two β subunits which are disulfide-linked into an α2β2 heterotetrameric complex (Figure 1). The receptor subunits are initially synthesized as αβ polypeptide fusion precursor proteins which undergoes extensive co-and post-translational modifications8–12. The receptor Mr 155,000 αβ precursors undergoe co-translational acylation and Asn-linked glycosylation. As the precursor is processed from the endoplasmic reticulum through the trans-Golgi network, intramolecular disulfide bonds are formed linking the a subunit to the β subunit. During this time frame, two αβ fusion precursors non-covalently dimerize followed by proteolytic cleavage at a furin-like tetrabasic sequence which separates the a subunit from the β subunit. Finally, the dimerized αβ half-receptors become disulfide-linked through the a subunits coincident with the addition of terminal sialic acid residues and exposure of the native α2β2 heterotetrameric receptor on the cell surface membrane.

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  1. Department of Physiology & Biophysics, The University of Iowa, Iowa City, Iowa, USA

    Jeffrey E. Pessin

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  1. National Institutes of Health, Bethesda, Maryland, USA

    Derek Le Roith M.D., Ph.D.

  2. University of Florida, Gainesville, Florida, USA

    Mohan K. Raizada Ph.D.

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Pessin, J.E. (1994). Molecular Properties of Insulin/IGF-1 Hybrid Receptors 4th International Symposium on Insulin, IGFs and Their Receptors. In: Le Roith, D., Raizada, M.K. (eds) Current Directions in Insulin-Like Growth Factor Research. Advances in Experimental Medicine and Biology, vol 343. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2988-0_14

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  • DOI: https://doi.org/10.1007/978-1-4615-2988-0_14

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