Molecular mechanisms underlying insulin-like growth factor action how mutations in the GH: IGF axis lead to short stature

Pediatric Endocrinology Reviews

Volumn 8, Issue 4, 2011, Pages 374-381

  Forbes, Briony E ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Growth hormone; IGF 1 mutations; IGF 1R; IGF 1R mutations; Insulin like growth factor

Indexed keywords

GROWTH HORMONE; INSULIN; INSULIN RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN TYROSINE KINASE; SOMATOMEDIN B RECEPTOR; SOMATOMEDIN BINDING PROTEIN 3; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; HUMAN GROWTH HORMONE; SOMATOMEDIN B;

BINDING AFFINITY; CELL DIFFERENTIATION; CELL GROWTH; CELL SURVIVAL; CRYSTAL STRUCTURE; EXON; GENE DELETION; GENE MUTATION; HORMONE RECEPTOR INTERACTION; HUMAN; METABOLIC REGULATION; MISSENSE MUTATION; NONHUMAN; PATHOGENESIS; PROTEIN BINDING; PROTEIN CROSS LINKING; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; SHORT STATURE; AMINO ACID SEQUENCE; BODY HEIGHT; CHEMISTRY; CHILD; GENETICS; GROWTH DISORDER; METABOLISM; MOLECULAR GENETICS; PROTEIN TERTIARY STRUCTURE; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; BODY HEIGHT; CHILD; GROWTH DISORDERS; HUMAN GROWTH HORMONE; HUMANS; INSULIN-LIKE GROWTH FACTOR I; INSULIN-LIKE GROWTH FACTOR II; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, TERTIARY; RECEPTOR, IGF TYPE 1; RECEPTOR, IGF TYPE 2; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 80055089655     PISSN: 15654753     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (77)

1. Abuzzahab MJ, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E, Kiess W, Klammt J, Kratzsch J, Osgood D, Pfaffle R, Raile K, Seidel B, Smith RJ, Chernausek SD. IGF-1 receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med 2003;349(23):2211-2222 (Pubitemid 37485137)
2. Adams TE, Epa VC, Garrett TP, Ward CW. Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci 2000;57(7):1050-1093 (Pubitemid 30598754)
3. Alvino CL, Mcneil KA, Ong SC, Delaine C, Booker GW, Wallace JC, Whittaker J, Forbes BE. A Novel Approach to Identify Two Distinct Receptor Binding Surfaces of Insulin-like Growth Factor II. J Biol Chem 2009;284(12):7656-7664
4. Avnet S, Sciacca L, Salerno M, Gancitano G, Cassarino MF, Longhi A, Zakikhani M, Carboni JM, Gottardis M, Giunti A, Pollak M, Vigneri R, Baldini N. Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma. Cancer Res 2009;69(6):2443-2452
5. Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993;75(1):73-82 (Pubitemid 23306022)
6. Bonapace G, Concolino D, Formicola S, Strisciuglio P. A novel mutation in a patient with insulin-like growth factor 1 (IGF1) deficiency. J Med Genet 2003;40(12):913-917 (Pubitemid 38117542)
7. Brown J, Delaine C, Zaccheo OJ, Siebold C, Gilbert RJ, Van Boxel G, Denley A, Wallace JC, Hassan AB, Forbes BE, Jones EY. Structure and functional analysis of the IGF-11/IGF2R interaction. Embo J 2008;27(1):265-276
8. Brown J, Jones EY, Forbes BE. Interactions of IGF-11 with the IGF2R/- Cation-Independent Mannose-6-Phosphate Receptor Mechanism and Biological Outcomes. Vitam Horm 2009;80:699-719
9. Brown J, Jones EY, Forbes BE. Keeping IGF-11 under control: lessons from the IGF-11-IGF2R crystal structure. Trends Biochem Sci 2009;34(12):612-619
10. Choi JH, Kang M, Kim GH, Hong M, Jin HY, Lee BH, Park JY, Lee SM, Seo EJ, Yoo HW. Clinical and Functional Characteristics of a Novel Heterozygous Mutation of the IGF1R Gene and IGF1R Haploinsufficiency due to Terminal 15q26.2->qter Deletion in Patients with Intrauterine Growth Retardation and Postnatal Catch-Up Growth Failure. J Clin Endocrinol Metab 2011;96(1):E130-134
11. Constancia M, Hemberger M, Hughes J, Dean W, Ferguson-Smith A, Fundele R, Stewart F, Kelsey G, Fowden A, Sibley C, Reik W. Placental-specific IGF-11 is a major modulator of placental and fetal growth. Nature 2002;417(6892):945-948 (Pubitemid 34716870)
12. Coutinho DC, Coletta RR, Costa EM, Pacht PR, Boguszewski MC, Damiani D, Mendonca BB, Arnhold IJ, Jorge AA. Polymorphisms identified in the upstream core polyadenylation signal of IGF1 gene exon 6 do not cause pre- and postnatal growth impairment. J Clin Endocrinol Metab 2007;92(12):4889-4892 (Pubitemid 350223474)
13. De Meyts P. The structural basis of insulin and insulin-like growth factor-1 receptor binding and negative co-operativity, and its relevance to mitogenic versus metabolic signalling. Diabetologia 1994;37(Suppl 2):S135-148 (Pubitemid 24288803)
14. De Meyts P. Insulin and insulin-like growth factors: the paradox of signaling specificity. Growth Horm IGF Res 2002;12(2):81-83 (Pubitemid 37337005)
15. De Meyts P, Gauguin L, Svendsen AM, Sarhan M, Knudsen L, Nohr J, Kiselyov W. 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 2009;1160:45-53
16. De Meyts P, Whittaker J. Structural biology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov 2002;1(10):769-783 (Pubitemid 37361561)
17. Delaine C, Alvino CL, Mcneil KA, Mulhern TD, Gauguin L, De Meyts P, Jones EY, Brown J, Wallace JC, Forbes BE. A novel binding site for the human insulin-like growth factor-11 (IGF-11)/mannose 6-phosphate receptor on IGF-11. J Biol Chem 2007;282(26):18886-18894 (Pubitemid 47100168)
18. Denley A, Bonython ER, Booker GW, Cosgrove U, Forbes BE, Ward CW, Wallace JC. Structural determinants for high-affinity binding of insulin-like growth factor Il to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Mol Endocrinol 2004;18(10):2502-2512 (Pubitemid 39335984)
19. Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE. Molecular interactions of the IGF system. Cytokine Growth Factor Rev 2005;16(4-5):421-439 (Pubitemid 41022012)
20. Denley A, Wallace JC, Cosgrove U, Forbes BE. The Insulin Receptor Isoform Exon 11- (IR-A) in Cancer and other Diseases: A Review. Horm Metab Res 2003;35((11-12)):778-785 (Pubitemid 38058183)
21. Denley A, Wang CC, Mcneil KA, Walenkamp MJ, Van Duyvenvoorde H, Wit JM, Wallace JC, Norton RS, Karperien M, Forbes BE. Structural and functional characteristics of the Val44Met insulin-like growth factor I missense mutation: correlation with effects on growth and development. Mol Endocrinol 2005;19(3)711-721 (Pubitemid 40349442)
22. Domene HM, Scaglia PA, Jasper HG. Deficiency of the insulin-like growth factor-binding protein acid-labile subunit (ALS) of the circulating ternary complex in children with short stature. Pediatr Endocrinol Rev 2010;7(4):339-346
23. Ester WA, van Duyvenvoorde HA, De Wit CC, Broekman AJ, Ruivenkamp CA, Govaerts LC, Wit JM, Hokken-Koelega AC, Losekoot M. Two short children born small for gestational age with insulin-like growth factor 1 receptor haploinsufficiency illustrate the heterogeneity of its phenotype. J Clin Endocrinol Metab 2009;94(12):4717-4727
24. Fabry M, Schaefer E, Ellis L, Kojro E, Fahrenholz F, Brandenburg D. Detection of a new hormone contact site within the insulin receptor ectodomain by the use of a novel photoreactive insulin. J Biot Chem 1992;- 267(13):8950-8956
25. Fang P, Schwartz ID, Johnson BD, Derr MA, Roberts CT, Jr., Hwa V, Rosenfeld RG. Familial short stature caused by haploinsufficiency of the insulin-like growth factor i receptor due to nonsense-mediated messenger ribonucleic acid decay. J Clin Endocrinol Metab 2009;94(5):1740-1747
26. Favelyukis S, Till JH, Hubbard SR, Miller WT. Structure and autoregulation of the insulin-like growth factor 1 receptor kinase. Nat Struct Biot 2001;- 8(12):1058-1063
27. Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 2002;23(6):824-854 (Pubitemid 35454590)
28. Fofanova-Gambetti OV, Hwa V, Wit JM, Domene HM, Argente J, Bang P, Hogler W, Kirsch S, Pihoker C, Chiu HK, Cohen L, Jacobsen C, Jasper HG, Haeusler G, Campos-Barros A, Gallego-Gomez E, Gracia-Bouthelier R, Van Duyvenvoorde HA, Pozo J, Rosenfeld RG. Impact of heterozygosity for acid-labile subunit (IGFALS) gene mutations on stature: results from the international acid-labile subunit consortium. J Clin Endocrinol Metab 2010;95(9):4184-4191
29. Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol 1999;19(5):3278-3288 (Pubitemid 29193789)
30. Gauguin L. Structural basis for the specific interaction of insulin and insulin-like growth factors with their receptors. PhD Thesis 2008; The University of Copenhagen
31. Gauguin L, Delaine C, Alvino CL, Mcneil KA, Wallace JC, Forbes BE, De Meyts P. Alanine scanning of a putative receptor binding surface of insulin-like growth factor-1. J Biol Chem 2008;283(30):20821-20829
32. Gicquel C, Le Bouc Y. Hormonal regulation of fetal growth. Horm Res 2006;3:28-33 (Pubitemid 44689430)
33. Huang K, Chan SJ, Hua QX, Chu YC, Wang RY, Klaproth B, Jia W, Whittaker J, De Meyts P, Nakagawa SH, Steiner DF, Katsoyannis PG, Weiss MA. 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 2007;282(48):35337- 35349 (Pubitemid 350232427)
34. Huang K, Xu B, Hu SQ, Chu YC, Hua QX, Qu Y, Li B, Wang S, Wang RY, Nakagawa SH, Theede AM, Whittaker J, De Meyts P, Katsoyannis PG, Weiss MA. How insulin binds: the B-chain alpha-helix contacts the L, beta-helix of the insulin receptor. J Mol Biol 2004;341(2):529-550 (Pubitemid 38987787)
35. Inagaki K, Tiulpakov A, Rubtsov P, Sverdlova P, Peterkova V, Yakar S, Terekhov S, Leroith D. A familial insulin-like growth factor-1 receptor mutant leads to short stature: clinical and biochemical characterization. J Clin Endocrinol Metab 2007;92(4):1542-1548 (Pubitemid 46556437)
36. Jogie-Brahim S, Feldman D, Oh Y. Unraveling insulin-like growth factor binding protein-3 actions in human disease. Endocr Rev 2009;30(5):417-437
37. Kaku K, Osada H, Seki K, Sekiya S. Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth. Acta Paediatr 2007;96(3):363-367 (Pubitemid 46439493)
38. Kawashima Y, Kanzaki S, Yang F, Kinoshita T, Hanaki K, Nagaishi J, Ohtsuka Y, Hisatome I, Ninomoya H, Nanba E, Fukushima T, Takahashi S. Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation. J Clin Endocrinol Metab 2005;90(8):4679-4687 (Pubitemid 41159358)
39. Keyhanfar M, Booker GW, Whittaker J, Wallace JC, Forbes BE. Precise mapping of an IGF-1-binding site on the IGF-1R. Biochem J 2007;401(1):269-277 (Pubitemid 46114619)
40. Killian JK, Oka Y, Jang HS, Fu X, Waterland RA, Sohda T, Sakaguchi S, Jirtle RL. Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations. Hum Mutat 2001;18(1):25-31 (Pubitemid 32588475)
41. Kiselyov W, Versteyhe S, Gauguin L, De Meyts P. Harmonic oscillator model of the insulin and IGF1 receptors' allosteric binding and activation. Mol Syst Biol 2009;5(243):1-12
42. Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-1. Cytokine Growth Factor Rev 2006;17(4):305-323 (Pubitemid 44038612)
43. Kristensen C, Andersen AS, Ostergaard S, Hansen PH, Brandt J. Functional reconstitution of insulin receptor binding site from non-binding receptor fragments. J Biol Chem 2002;277(21):18340-18345 (Pubitemid 34952378)
44. Kruis T, Klammt J, Galli-Tsinopoulou A, Wallborn T, Schlicke M, Muller E, Kratzsch J, Korner A, Odeh R, Kiess W, Pfaffle R. Heterozygous mutation within a kinase-conserved motif of the insulin-like growth factor I receptor causes intrauterine and postnatal growth retardation. J Clin Endocrinol Metab 2010;95(3):1137-1142
45. Kurose T, Pashmforoush M, Yoshimasa Y, Carroll R, Schwartz GP, Burke GT, Katsoyannis PG, Steiner DF. Cross-linking of a B25 azidophenylalanine insulin derivative to the carboxyl-terminal region of the alpha-subunit of the insulin receptor. Identification of a new insulin-binding domain in the insulin receptor. J Biot Chem 1994;269(46):29190-29197
46. Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000;49(6):999-1005 (Pubitemid 30349423)
47. Laron Z. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. J Clin Endocrinol Metab 2004;89(3):1031-1044 (Pubitemid 38368385)
48. Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor 1 (IgM1) and type 1 IGF receptor (Igf1r). Cell 1993;75(1):59-72 (Pubitemid 23306021)
49. Mathews LS, Hammer RE, Brinster RL, Palmiter RD. Expression of insulin-like growth factor 1 in transgenic mice with elevated levels of growth hormone is correlated with growth. Endocrinology 1988;123(1):433-437
50. Mckern NM, Lawrence MC, Streltsov VA, Lou MZ, Adams TE, Lovrecz GO, Elleman TC, Richards KM, Bentley JD, Pilling PA, Hoyne PA, Cartledge KA, Pham TM, Lewis JL, Sankovich SE, Stoichevska V, Da Silva E, Robinson CP, Frenkel MJ, Sparrow LG, Fernley RT, Epa VC, Ward CW. Structure of the insulin receptor ectodomain reveals a folded-over conformation. Nature 2006;443(7108):218-221 (Pubitemid 44387610)
51. Nanjo K, Sanke T, Miyano M, Okai K, Sowa R, Kondo M, Nishimura S, Iwo K, Miyamura K, Given BD, Et Al. Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin. J Clin Invest 1986;77(2):514-519 (Pubitemid 16037651)
52. Netchine I, Azzi S, Houang M, Seurin D, Perin L, Ricort JM, Daubas C, Legay C, Mester J, Herich R, Godeau F, Le Bouc Y. Partial primary deficiency of insulin-like growth factor (IGF)-1 activity associated with IGF1 mutation demonstrates its critical role in growth and brain development. J Clin Endocrinol Metab 2009;94(10):3913-3921
53. Okubo Y, Siddle K, Firth H, O'rahilly S, Wilson LC, Willatt L, Fukushima T, Takahashi S, Petry CJ, Saukkonen T, Stanhope R, Dunger DB. Cell proliferation activities on skin fibroblasts from a short child with absence of one copy of the type 1 insulin-like growth factor receptor (IGF1R) gene and a tall child with three copies of the IGF1R gene. J Clin Endocrinol Metab 2003;88(12):5981-5988 (Pubitemid 38033082)
54. Pugliese-Pires PN, Tonelli CA, Dora JM, Silva PC, Czepielewski M, Simoni G, Arnhold IJ, Jorge AA. A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings. Eur J Endocrinol 2010;163(2):349-355
55. Raile K, Klammt J, Schneider A, Keller A, Laue S, Smith R, Pfaffle R, Kratzsch J, Keller E, Kiess W. Clinicat and functional characteristics of the human Arg59Ter insulin-like growth factor i receptor (IGF1R) mutation: implications for a gene dosage effect of the human IGF1R. J Clin Endocrinol Metab 2006;91(6):2264-2271 (Pubitemid 43855016)
56. Rosenfeld RG, Belgorosky A, Camacho-Hubner C, Savage MO, Wit JM, Hwa V. Defects in growth hormone receptor signaling. Trends Endocrinol Metab 2007;18(4):134-141 (Pubitemid 46629026)
57. Sciacca L, Mineo R, Pandini G, Murabito A, Vigneri R, Belfiore A. In IGF-1 receptor-deficient leiomyosarcoma cells autocrine IGF-11 induces cell invasion and protection from apoptosis via the insulin receptor isoform A. Oncogene 2002;21(54):8240-8250 (Pubitemid 35477864)
58. Smith BJ, Huang K, Kong G, Chan SJ, Nakagawa S, Menting JG, Hu SQ, Whittaker J, Steiner DF, Katsoyannis PG, Ward CW, Weiss MA, Lawrence MC. 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 2010;107(15):6771-6776
59. Sorensen H, Whittaker L, Hinrichsen J, Groth A, Whittaker J. Mapping of the insulin-like growth factor II binding site of the Type I insulin-like growth factor receptor by alanine scanning mutagenesis. FEBS Lett 2004;565(1-3):19-22 (Pubitemid 38595313)
60. Surinya KH, Molina L, Soos MA, Brandt J, Kristensen C, Siddle K. Role of insulin receptor dimerization domains in ligand binding, cooperativity, and modulation by anti-receptor antibodies. J Biol Chem 2002;277(19):16718-16725 (Pubitemid 34967692)
61. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 2006;7(2):85-96 (Pubitemid 43278292)
62. Walenkamp MJ, Karperien M, Pereira AM, Hilhorst-Hofstee Y, Van Doorn J, Chen JW, Mohan S, Denley A, Forbes B, Van Duyvenvoorde HA, Van Thiel SW, Sluimers CA, Bax JJ, De Laat JA, Breuning MB, Romijn JA, Wit JM. Homozygous and heterozygous expression of a novel insulin-like growth factor-1 mutation. J Clin Endocrinol Metab 2005;90(5):2855-2864 (Pubitemid 40686336)
63. Walenkamp MJ, Van Der Kamp HJ, Pereira AM, Kant SG, Van Duyvenvoorde HA, Kruithof MF, Breuning MH, Romijn JA, Karperien M, Wit JM. A variable degree of intrauterine and postnatal growth retardation in a family with a missense mutation in the insulin-like growth factor I receptor. J Clin Endocrinol Metab 2006;91(8):3062-3070 (Pubitemid 44271756)
64. Walenkamp MJ, Wit JM. Genetic disorders in the GH IGF-1 axis in mouse and man. Eur J Endocrinol 2007;157Suppl 1:S15-26 (Pubitemid 47434126)
65. Walenkamp MJ, Wit JM. Single gene mutations causing SGA. Best Pract Res Clin Endocrinol Metab 2008;22(3):433-446 (Pubitemid 351766605)
66. Wallborn T, Wuller S, Klammt J, Kruis T, Kratzsch J, Schmidt G, Schlicke M, Muller E, Van De Leur HS, Kiess W, Pfaffle R. A heterozygous mutation of the insulin-like growth factor-1 receptor causes retention of the nascent protein in the endoplasmic reticulum and results in intrauterine and postnatal growth retardation. J Clin Endocrinol Metab 2010;95(5):2316-2324
67. Wan Z, Xu B, Huang K, Chu YC, Li B, Nakagawa SH, Qu Y, Hu SQ, Katsoyannis PG, Weiss MA. Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues. Biochemistry 2004;43(51):16119-16133 (Pubitemid 40041025)
68. Wan ZL, Huang K, Xu B, Hu SQ, Wang S, Chu YC, Katsoyannis PG, Weiss MA. Diabetes-associated mutations in human insulin: crystal structure and photo-cross-linking studies of a-chain variant insulin Wakayama. Biochemistry 2005;44(13):5000-5016 (Pubitemid 40471216)
69. Ward C, Lawrence M, Streltsov V, Garrett T, Mckern N, Lou MZ, Lovrecz G, Adams T. Structural insights into ligand-induced activation of the insulin receptor. Acta Physiol (Oxf) 2008;192(1):3-9 (Pubitemid 350265361)
70. Ward CW, Lawrence MC. Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor. Bioessays 2009;31(4):422-434
71. Whittaker J, Groth AV, Mynarcik DC, Pluzek L, Gadsboll VL, Whittaker LJ. Alanine scanning mutagenesis of a type 1 insulin-like growth factor receptor ligand binding site. J Biol Chem 2001;276(47):43980-43986
72. Whittaker J, Sorensen H, Gadsboll VL, Hinrichsen J. Comparison of the functional insulin binding epitopes of the A and B isoforms of the insulin receptor. J Biol Chem 2002;277(49):47380-47384 (Pubitemid 36159252)
73. Whittaker L, Hao C, Fu W, Whittaker J. High-Affinity Insulin Binding: Insulin Interacts with Two Receptor Ligand Binding Sites. Biochemistry 2008;47(48):12900-12909
74. Wit JM, Clayton PE, Rogol AD, Savage MO, Saenger PH, Cohen P. Idiopathic short stature: definition, epidemiology, and diagnostic evaluation. Growth Horm IGF Res 2008;18(2):89-110 (Pubitemid 351292522)
75. Woods KA, Camacho-Hubner C, Savage MO, Clark AJ. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor 1 gene. N Engl J Med 1996;335(18):1363-1367 (Pubitemid 26360455)
76. Xu B, Hu SQ, Chu YC, Huang K, Nakagawa SH, Whittaker J, Katsoyannis PG, Weiss MA. Diabetes-Associated Mutations in Insulin: Consecutive Residues in the B Chain Contact Distinct Domains of the Insulin Receptor(,). Biochemistry 2004;43(26):8356-8372 (Pubitemid 38902515)
77. Zhang W, Gustafson TA, Rutter WJ, Johnson JD. Positively charged side chains in the insulin-like growth factor-1 C- and D-regions determine receptor binding specificity. J Biol Chem 1994;269(14):10609-10613 (Pubitemid 24198264)