Insight into the molecular basis for the kinetic differences between the two insulin receptor isoforms

Biochemical Journal

Volumn 440, Issue 3, 2011, Pages 397-403

  Knudsen, Louise ^a   De Meyts, Pierre ^a,b   Kiselyov, Vladislav V ^a  

^a HAGEDORN RESEARCH INSTITUTE   (Denmark)

^b De Meyts R and D Consulting SPRLU   (Belgium)

Author keywords

Binding kinetics; Harmonic oscillator; Insulin; Insulin receptor; Insulin receptor lacking exon 11 (IR A); Insulin receptor with exon 11 (IR B); Mathematical modelling

Indexed keywords

INSULIN RECEPTOR; ISOPROTEIN;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING SITE; DISSOCIATION CONSTANT; EXON; HUMAN; HUMAN CELL; LIGAND BINDING; MATHEMATICAL ANALYSIS; MITOGENESIS; PRIORITY JOURNAL; RECEPTOR AFFINITY;

ALTERNATIVE SPLICING; AMINO ACID MOTIFS; ANIMALS; BINDING SITES; BINDING, COMPETITIVE; CHO CELLS; CRICETINAE; HUMANS; INSULIN; ISOENZYMES; KINETICS; MODELS, MOLECULAR; PROTEIN BINDING; RECEPTOR, INSULIN; RECOMBINANT PROTEINS;

EID: 82455186745     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20110550     Document Type: Article

References (51)

1. Belfiore, A., Frasca, F., Pandini, G., Sciacca, L. and Vigneri, R. (2009) Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr. Rev. 30, 586-623
2. De Meyts, P. and Whittaker, J. (2002) Structural biology of insulin and IGF1 receptors: implications for drug design. Nat. Rev. Drug Discovery 1, 769-783 (Pubitemid 37361561)
3. Adams, T. E., Epa, V. C., Garrett, T. P. J. and Ward, C. W. (2000) Structure and function of the type 1 insulin-like growth factor receptor. Cell. Mol. Life Sci. 57, 1050-1093 (Pubitemid 30598754)
4. Ullrich, A., Bell, J. R., Chen, E. Y., Herrera, R., Petruzzelli, L. M., Dull, T. J., Gray, A., Coussens, L., Liao, Y. C., Tsubokawa, M. et al. (1985) Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313, 756-761 (Pubitemid 15130823)
5. Ebina, Y., Ellis, L., Jarnagin, K., Edery, M., Graf, L., Clauser, E., Ou, J. H., Masiarz, F., Kan, Y. W., Goldfine, I. D. et al. (1985) The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell 40, 747-758 (Pubitemid 15240280)
6. Seino, S., Seino, M., Nishi, S. and Bell, G.I. (1989) Structure of the human insulin receptor gene and characterization of its promoter. Proc. Natl. Acad. Sci. U.S.A. 86, 114-118 (Pubitemid 19036344)
7. Moller, D. E., Yokota, A., Caro, J. F. and Flier, J. S. (1989) Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. Mol. Endocrinol. 3, 1263-1269 (Pubitemid 19210437)
8. Mosthaf, L., Grako, K., Dull, T. J., Coussens, L., Ullrich, A. and McClain, D. A. (1990) Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J. 9, 2409-2413
9. Seino, S. and Bell, G. I. (1989) Alternative splicing of human insulin receptor messenger RNA. Biochem. Biophys. Res. Commun. 159, 312-316 (Pubitemid 19087646)
10. Goldstein, B. J. and Dudley, A. L. (1990) The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing. Mol. Endocrinol. 4, 235-244
11. Lou, Y., Zee, R. Y. L., Li, M. and Morris, B. J. (1998) Insulin receptor exon 11+/- isoform mRNA in spontaneously hypertensive and adrenocorticotropin- hypertensive rats. J. Hypertens. 16, 1009-1014 (Pubitemid 28367956)
12. Vidal, H., Auboeuf, D., Beylot, M. and Riou, J. P. (1995) Regulation of insulin receptor mRNA splicing in rat tissues. Diabetes 44, 1196-1201
13. Benecke, H., Flier, J. S. and Moller, D. E. (1992) Alternatively spliced variants of the insulin receptor protein. J. Clin. Invest 89, 2066-2070
14. Anderson, C. M., Henry, R. R., Knudson, P. E., Olefsky, J. M. and Webster, N. J. G. (1993) Relative expression of insulin receptor isoforms does not differ in lean, obese, and noninsulin-dependent diabetes mellitus subjects. J. Clin. Endocrinol. Metab. 76, 1380-1382 (Pubitemid 23155469)
15. Hansen, T., Bjørbaek, C., Vestergaard, H., Grønskov, K., Bak, J. F. and Pedersen, O. (1993) Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 77, 1500-1505 (Pubitemid 24000903)
16. Huang, Z., Bodkin, N. L., Ortmeyer, H. K., Hansen, B. C. and Shuldiner, A. R. (1994) Hyperinsulinemia is associated with altered insulin receptor mRNA splicing in muscle of the spontaneously obese diabetic rhesus monkey. J. Clin. Invest 94, 1289-1296 (Pubitemid 24286474)
17. McGrattan, P. D., Wylie, A. R. G. and Bjourson, A. J. (1998) A partial cDNA sequence of the ovine insulin receptor gene: evidence for alternative splicing of an exon 11 region and for tissue-specific regulation of receptor isoform expression in sheep muscle, adipose tissue and liver. J. Endocrinol. 159, 381-387 (Pubitemid 29003013)
18. Yamaguchi, Y., Flier, J. S., Benecke, H., Ransil, B. J. and Moller, D. E. (1993) Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology 132, 1132-1138 (Pubitemid 23068628)
19. Benyoucef, S., Surinya, K. H., Hadaschik, D. and Siddle, K. (2007) Characterization of insulin/IGF hybrid receptors: Contributions of the insulin receptor L2 and Fn1 domains and the alternatively spliced exon 11 sequence to ligand binding and receptor activation. Biochem. J. 403, 603-613 (Pubitemid 46706989)
20. Giudice, J., Leskow, F. C., Arndt-Jovin, D. J., Jovin, T. M. and Jares-Erijman, E. A. (2011) Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B. J. Cell Sci. 124, 801-811
21. McClain, D., Mosthaf, L. and Ulrich, A. (1989) Properties of the two naturally occuring alternate forms of the insulin receptor. Diabetes 38 (Suppl. 1), abstract number 1
22. Gu, J. L. and De Meyts, P. (1991) The structure and function of insulin receptor. Retrospect and Prospect of Protein Research (Zai-ping, L., Zi xian, L. and You shang, Z. eds.), pp. 120-125, World Scientific, Singapore
23. Yamaguchi, Y., Flier, J. S., Yokota, A., Benecke, H., Backer, J. M. and Moller, D. E. (1991) Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology 129, 2058-2066
24. Whittaker, J., Sørensen, H., Gadsbøll, V. L. and Hinrichsen, J. (2002) Comparison of the functional insulin binding epitopes of the A and B isoforms of the insulin receptor. J. Biol. Chem. 277, 47380-47384 (Pubitemid 36159252)
25. Gu, J. L., Shymko, R. M., Wallach, B., Whittaker, J. and De Meyts, P. (1990) Receptor binding properties of the two natural variants of the insulin receptor. Diabetes 39 (Suppl. 1), 79A
26. Denley, A., Bonython, E. R., Booker, G. W., Cosgrove, L. J., Forbes, B. E., Ward, C. W. and Wallace, J. C. (2004) Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Mol. Endocrinol. 18, 2502-2512 (Pubitemid 39335984)
27. McClain, D. A. (1991) Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action. Mol. Endocrinol. 5, 734-739
28. Vogt, B., Carrascosa, J. M., Ermel, B., Ullrich, A. and Häring, H. U. (1991) The two isotypes of the human insulin receptor (HIR-A and HIR-B) follow different internalization kinetics. Biochem. Biophys. Res. Commun. 177, 1013-1018
29. Pandini, G., Frasca, F., Mineo, R., Sciacca, L., Vigneri, R. and Belfiore, A. (2002) Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J. Biol. Chem. 277, 39684-39695 (Pubitemid 35190951)
30. Slaaby, R., Schaffer, L., Lautrup-Larsen, I., Andersen, A. S., Shaw, A. C., Mathiasen, I. S. and Brandt, J. (2006) Hybrid receptors formed by insulin receptor (IR) and insulin- like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. J. Biol. Chem. 281, 25869-25874 (Pubitemid 44401792)
31. Kiselyov, V. V., Versteyhe, S., Gauguin, L. and De Meyts, P. (2009) Harmonic oscillator model of the insulin and IGF1 receptors' allosteric binding and activation. Mol. Sys. Biol. 5, 243
32. De Meyts, P. (1994) The structural basis of insulin and insulin-like growth factor-I receptor binding and negative co-operativity, and its relevance to mitogenic versus metabolic signalling. Diabetologia 37 (Suppl. 2), S135-S148
33. De Meyts, P. (2004) Insulin and its receptor: structure, function and evolution. BioEssays 26, 1351-1362
34. Schäffer, L. (1994) A model for insulin binding to the insulin receptor. Eur. J. Biochem. 221, 1127-1132
35. McKern, N. M., Lawrence, M. C., Streltsov, V. A., Lou, M. Z., Adams, T. E., Lovrecz, G. O., Elleman, T. C., Richards, K. M., Bentley, J. D., Pilling, P. A. et al. (2006) Structure of the insulin receptor ectodomain reveals a folded-over conformation. Nature 443, 218-221 (Pubitemid 44387610)
36. Kurose, T., Pashmforoush, M., Yoshimasa, Y., Carroll, R., Schwartz, G. P., Burke, G. T., Katsoyannis, P. G. and Steiner, D. F. (1994) Cross-linking of a B25 azidophenylalanine insulin derivative to the carboxyl-terminal region of the α-subunit of the insulin receptor: identification of a new insulin-binding domain in the insulin receptor. J. Biol. Chem. 269, 29190-29197
37. Huang, K., Xu, B., Hu, S. Q., Chu, Y. C., Hua, Q. X., Qu, Y., Li, B., Wang, S., Wang, R. Y., Nakagawa, S. H. et al. (2004) How insulin binds: the B-chain α-helix contacts the L1 β-helix of the insulin receptor. J. Mol. Biol. 341, 529-550 (Pubitemid 38987787)
38. Huang, K., Chan, S. J., Hua, Q. X., Chu, Y. C., Wang, R. Y., Klaproth, B., Jia, W. H., Whittaker, J., De Meyts, P., Nakagawa, S. H. et al. (2007) The A-chain of insulin contacts the insert domain of the insulin receptor: photo-cross-linking and mutagenesis of a diabetes-related crevice. J. Biol. Chem. 282, 35337-35349 (Pubitemid 350232427)
39. Xu, B., Hu, S. Q., Chu, Y. C., Huang, K., Nakagawa, S. H., Whittaker, J., Katsoyannis, P. G. and Weiss, M. A. (2004) Diabetes-associated mutations in insulin: consecutive residues in the B chain contact distinct domains of the insulin receptor. Biochemistry 43, 8356-8372 (Pubitemid 38902515)
40. Williams, P. F., Mynarcik, D. C., Yu, G. Q. and Whittaker, J. (1995) Mapping of an NH2-terminal ligand binding site of the insulin receptor by alanine scanning mutagenesis. J. Biol. Chem. 270, 3012-3016
41. Mynarcik, D. C., Yu, G. Q. and Whittaker, J. (1996) Alanine-scanning mutagenesis of a C-terminal ligand binding domain of the insulin receptor α subunit. J. Biol. Chem. 271, 2439-2442 (Pubitemid 26047846)
42. Hao, C., Whittaker, L. and Whittaker, J. (2006) Characterization of a second ligand binding site of the insulin receptor. Biochem. Biophys. Res. Commun. 347, 334-339 (Pubitemid 44015681)
43. De Meyts, P. (2008) The insulin receptor: a prototype for dimeric, allosteric membrane receptors? Trends Biochem. Sci. 33, 376-384
44. De Meyts, P., Gauguin, L., Svendsen, A. M., Sarhan, M., Knudsen, L., Nøhr, J. and Kiselyov, V. V. (2009) Structural basis of allosteric ligand-receptor interactions in the insulin-relaxin peptide family: implications for other receptor tyrosine kinases and G-protein-coupled receptors. Ann. N.Y. Acad. Sci. 1160, 45-53
45. Whittaker, L., Hao, C., Fu, W. and Whittaker, J. (2008) High affinity insulin binding: insulin interacts with two receptor ligand binding sites. Biochemistry 47, 12900-12909
46. Smith, B. J., Huang, K., Kong, G., Chan, S. J., Nakagawa, S., Menting, J. G., Hu, S. Q., Whittaker, J., Steiner, D. F., Katsoyannis, P. G. et al. (2010) Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists. Proc. Natl. Acad. Sci. U.S.A. 107, 6771-6776
47. Vashisth, H. and Abrams, C. F. (2010) Docking of insulin to a structurally equilibrated insulin receptor ectodomain. Proteins 78, 1531-1543
48. Hansen, B. F., Danielsen, G. M., Drejer, K., Sørensen, A. R., Wiberg, F. C., Klein, H. H. and Lundemose, A. G. (1996) Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem. J. 315, 271-279 (Pubitemid 26113562)
49. Shymko, R. M., De Meyts, P. and Thomas, R. (1997) Logical analysis of timing-dependent receptor signalling specificity: application to the insulin receptor metabolic and mitogenic signalling pathways. Biochem. J. 326, 463-469 (Pubitemid 27417224)
50. Jensen, M., Hansen, B., De Meyts, P., Schäffer, L. and Ursø, B. (2007) Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses. J. Biol. Chem. 282, 35179-35186 (Pubitemid 350232483)
51. Jensen, M. and De Meyts, P. (2009) Molecular mechanisms of differential intracellular signaling from the insulin receptor. Vitam. Horm. 80, 51-75