Molecular interactions of the IGF system

Cytokine & Growth Factor Reviews - Tập 16 - Trang 421-439 - 2005
Adam Denley1,2, Leah J. Cosgrove2, Grant W. Booker1, John C. Wallace1, Briony E. Forbes1
1School of Molecular and Biomedical Science, The University of Adelaide, SA 5005, Australia
2CSIRO Division of Health Sciences and Nutrition, Adelaide, Australia

Tài liệu tham khảo

Khandwala, 2000, The effects of insulin-like growth factors on tumorigenesis and neoplastic growth, Endocr Rev, 21, 215, 10.1210/er.21.3.215 Pollak, 2004, Insulin-like growth factors and neoplasia, Nat Rev Cancer, 4, 505, 10.1038/nrc1387 Baumann, 2002, Genetic characterization of growth hormone deficiency and resistance: implications for treatment with recombinant growth hormone, Am J Pharmacogenomics, 2, 93, 10.2165/00129785-200202020-00003 Laron, 2004, Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience, J Clin Endocrinol Metab, 89, 1031, 10.1210/jc.2003-031033 O’Connor, 2003, Regulation of IGF-I receptor signaling in tumor cells, Horm Metab Res, 35, 771, 10.1055/s-2004-814166 Kim, 2002, Signalling through IGF-I and insulin receptors: where is the specificity?, Growth Horm IGF Res, 12, 84, 10.1054/ghir.2002.0265 Rinderknecht, 1978, The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin, J Biol Chem, 253, 2769, 10.1016/S0021-9258(17)40889-1 Cooke, 1991, Solution structure of human insulin-like growth factor 1: a nuclear magnetic resonance and restrained molecular dynamics study, Biochemistry, 30, 5484, 10.1021/bi00236a022 Sato, 1993, Three-dimensional structure of human insulin-like growth factor-I (IGF-I) determined by 1H-NMR and distance geometry, Int J Pept Protein Res, 41, 433, 10.1111/j.1399-3011.1993.tb00462.x Schaffer, 2003, Complex with a phage display-derived peptide provides insight into the function of insulin-like growth factor I, Biochemistry, 42, 9324, 10.1021/bi034386c Vajdos, 2001, Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions, Biochemistry, 40, 11022, 10.1021/bi0109111 Zeslawski, 2001, The interaction of insulin-like growth factor-I with the N-terminal domain of IGFBP-5, EMBO J, 20, 3638, 10.1093/emboj/20.14.3638 Brzozowski, 2002, Structural origins of the functional divergence of human insulin-like growth factor-I and insulin, Biochemistry, 41, 9389, 10.1021/bi020084j Siwanowicz, 2005, Structural basis for the regulation of insulin-like growth factors by IGF binding proteins, Structure, 13, 155, 10.1016/j.str.2004.11.009 Terasawa, 1994, Solution structure of human insulin-like growth factor II; recognition sites for receptors and binding proteins, EMBO J, 13, 5590, 10.1002/j.1460-2075.1994.tb06896.x Torres, 1995, Solution structure of human insulin-like growth factor II. Relationship to receptor and binding protein interactions, J Mol Biol, 248, 385, 10.1016/S0022-2836(95)80058-1 Bentley, 1976, Structure of insulin in 4-zinc insulin, Nature, 261, 166, 10.1038/261166a0 Baker, 1988, The structure of 2Zn pig insulin crystals at 1.5 A resolution, Philos Trans R Soc Lond B Biol Sci, 319, 369, 10.1098/rstb.1988.0058 Weiss, 1990, NMR and photo-CIDNP studies of human proinsulin and prohormone processing intermediates with application to endopeptidase recognition, Biochemistry, 29, 8389, 10.1021/bi00488a028 Walenkamp, 2005, Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation, J Clin Endocrinol Metab, 90, 2855, 10.1210/jc.2004-1254 Denley, 2005, Structural and functional characteristics of the Val44Met insulin-like growth factor I missense mutation: correlation with effects on growth and development, Mol Endocrinol, 19, 711, 10.1210/me.2004-0409 Woods, 1997, Insulin-like growth factor I gene deletion causing intrauterine growth retardation and severe short stature, Acta Paediatr Suppl, 423, 39, 10.1111/j.1651-2227.1997.tb18367.x Liu, 1993, Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r), Cell, 75, 59 DeChiara, 1990, A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting, Nature, 345, 78, 10.1038/345078a0 Pandini, 2003, Differential gene expression induced by insulin and insulin-like growth factor-II through the insulin receptor isoform A, J Biol Chem, 278, 42178, 10.1074/jbc.M304980200 Pandini, 2004, Igf-ii binding to insulin receptor isoform a induces a partially different gene expression profile from insulin binding, Ann NY Acad Sci, 450, 10.1196/annals.1322.053 Nakae, 2001, Distinct and overlapping functions of insulin and IGF-I receptors, Endocr Rev, 22, 818, 10.1210/er.22.6.818 Denley, 2003, The insulin receptor isoform exon 11− (IR-A) in cancer and other diseases: a review, Horm Metab Res, 35, 778, 10.1055/s-2004-814157 Sesti, 2000, Insulin receptor variant forms and type 2 diabetes mellitus, Pharmacogenomics, 1, 49, 10.1517/14622416.1.1.49 Pandini, 1999, Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: evidence for a second mechanism of IGF-I signaling, Clin Cancer Res, 5, 1935 Adams, 2000, Structure and function of the type 1 insulin-like growth factor receptor, Cell Mol Life Sci, 57, 1050, 10.1007/PL00000744 Czech, 1982, Structural and functional homologies in the receptors for insulin and the insulin-like growth factors, Cell, 31, 8, 10.1016/0092-8674(82)90399-3 Bhaumick, 1981, Somatomedin receptor of human placenta: solubilization, photolabeling, partial purification, and comparison with insulin receptor, Proc Natl Acad Sci USA, 78, 4279, 10.1073/pnas.78.7.4279 Chernausek, 1981, Structural similarities between human receptors for somatomedin C and insulin: analysis by affinity labeling, Biochemistry, 20, 7345, 10.1021/bi00529a004 Siddle, 2001, Specificity in ligand binding and intracellular signalling by insulin and insulin-like growth factor receptors, Biochem Soc Trans, 29, 513, 10.1042/bst0290513 De Meyts, 2002, Structural biology of insulin and IGF1 receptors: implications for drug design, Nat Rev Drug Discov, 1, 769, 10.1038/nrd917 Schaefer, 1990, Deletion analysis of the human insulin receptor ectodomain reveals independently folded soluble subdomains and insulin binding by a monomeric alpha-subunit, J Biol Chem, 265, 13248, 10.1016/S0021-9258(19)38291-2 Brandt, 2001, Dimeric fragment of the insulin receptor alpha-subunit binds insulin with full holoreceptor affinity, J Biol Chem, 276, 12378, 10.1074/jbc.M009402200 Kasuga, 1982, Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor, Science, 215, 185, 10.1126/science.7031900 Rubin, 1983, Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I, Nature, 305, 438, 10.1038/305438a0 Garrett, 1998, Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor, Nature, 394, 395, 10.1038/28668 Schumacher, 1991, Insulin and insulin-like growth factor-1 binding specificity is determined by distinct regions of their cognate receptors, J Biol Chem, 266, 19288, 10.1016/S0021-9258(18)54996-6 Whittaker, 2001, Alanine scanning mutagenesis of a type 1 insulin-like growth factor receptor ligand binding site, J Biol Chem, 276, 43980, 10.1074/jbc.M102863200 Sorensen, 2004, 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, 565, 19, 10.1016/j.febslet.2004.03.077 Andersen, 1990, Changing the insulin receptor to possess insulin-like growth factor I ligand specificity, Biochemistry, 29, 7363, 10.1021/bi00484a002 Kjeldsen, 1991, The ligand specificities of the insulin receptor and the insulin-like growth factor I receptor reside in different regions of a common binding site, Proc Natl Acad Sci USA, 88, 4404, 10.1073/pnas.88.10.4404 Wedekind, 1989, Hormone binding site of the insulin receptor: analysis using photoaffinity-mediated avidin complexing, Biol Chem Hoppe Seyler, 370, 251, 10.1515/bchm3.1989.370.1.251 Fabry, 1992, Detection of a new hormone contact site within the insulin receptor ectodomain by the use of a novel photoreactive insulin, J Biol Chem, 267, 8950, 10.1016/S0021-9258(19)50372-6 Kurose, 1994, 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 Biol Chem, 269, 29190, 10.1016/S0021-9258(19)62029-6 Williams, 1995, Mapping of an NH2-terminal ligand binding site of the insulin receptor by alanine scanning mutagenesis, J Biol Chem, 270, 3012, 10.1074/jbc.270.7.3012 Mynarcik, 1996, Alanine-scanning mutagenesis of a C-terminal ligand binding domain of the insulin receptor alpha subunit, J Biol Chem, 271, 2439, 10.1074/jbc.271.5.2439 Whittaker, 2002, Comparison of the functional insulin binding epitopes of the A and B isoforms of the insulin receptor, J Biol Chem, 277, 47380, 10.1074/jbc.M208371200 Firth, 2002, Cellular actions of the insulin-like growth factor binding proteins, Endocr Rev, 23, 824, 10.1210/er.2001-0033 Clemmons, 2001, Use of mutagenesis to probe IGF-binding protein structure/function relationships, Endocr Rev, 22, 800, 10.1210/er.22.6.800 Frystyk, 2004, Free insulin-like growth factors – measurements and relationships to growth hormone secretion and glucose homeostasis, Growth Horm IGF Res, 14, 337, 10.1016/j.ghir.2004.06.001 Baxter, 2000, Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities, Am J Physiol Endocrinol Metab, 278, E967, 10.1152/ajpendo.2000.278.6.E967 Hwa, 1999, The insulin-like growth factor-binding protein (IGFBP) superfamily, Endocr Rev, 20, 761, 10.1210/er.20.6.761 Carrick, 2001, The interaction of insulin-like growth factors (IGFs) with insulin-like growth factor binding proteins (IGFBPs): a review, Lett Pept Sci, 8, 147, 10.1007/BF02446511 Headey, 2004, C-terminal domain of insulin-like growth factor binding protein-6: structure and interaction with insulin-like growth factor-II, Mol Endocrinol, 10.1210/me.2004-0248 Headey, 2004, Binding site for the C-domain of insulin-like growth factor (IGF) binding protein-6 on IGF-II; implications for inhibition of IGF actions, FEBS Lett, 568, 19, 10.1016/j.febslet.2004.04.091 Scott, 2004, The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal?, Horm Metab Res, 36, 261, 10.1055/s-2004-814477 De Souza, 1995, M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity, Nat Genet, 11, 447, 10.1038/ng1295-447 Oka, 2002, M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan, Hepatology, 35, 1153, 10.1053/jhep.2002.32669 Jamieson, 2003, M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis, BMC Cancer, 3, 4, 10.1186/1471-2407-3-4 Lee, 1986, Identification of receptors for insulin-like growth factor II in two insulin-like growth factor II producing cell lines, Biochem Biophys Res Commun, 134, 595, 10.1016/S0006-291X(86)80461-2 Ewton, 1987, The type II insulin-like growth factor (IGF) receptor has low affinity for IGF-I analogs: pleiotypic actions of IGFs on myoblasts are apparently mediated by the type I receptor, Endocrinology, 120, 115, 10.1210/endo-120-1-115 Tong, 1988, The cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II, J Biol Chem, 263, 2585, 10.1016/S0021-9258(18)69105-7 Morgan, 1987, Insulin-like growth factor II receptor as a multifunctional binding protein, Nature, 329, 301, 10.1038/329301a0 Oshima, 1988, The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells, J Biol Chem, 263, 2553, 10.1016/S0021-9258(18)69243-9 Kornfeld, 1992, Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors, Annu Rev Biochem, 61, 307, 10.1146/annurev.bi.61.070192.001515 Devi, 1998, An insulin-like growth factor II (IGF-II) affinity-enhancing domain localized within extracytoplasmic repeat 13 of the IGF-II/mannose 6-phosphate receptor, Mol Endocrinol, 12, 1661, 10.1210/me.12.11.1661 Tong, 1989, Ligand interactions of the cation-independent mannose 6-phosphate receptor. The stoichiometry of mannose 6-phosphate binding, J Biol Chem, 264, 7962, 10.1016/S0021-9258(18)83136-2 Westlund, 1991, The bovine mannose 6-phosphate/insulin-like growth factor II receptor. Localization of mannose 6-phosphate binding sites to domains 1–3 and 7–11 of the extracytoplasmic region, J Biol Chem, 266, 23233, 10.1016/S0021-9258(18)54487-2 Brown, 2002, Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur, EMBO J, 21, 1054, 10.1093/emboj/21.5.1054 Garmroudi, 1994, Localization of the insulin-like growth factor II (IGF-II) binding/cross-linking site of the IGF-II/mannose 6-phosphate receptor to extracellular repeats 10–11, J Biol Chem, 269, 26944, 10.1016/S0021-9258(18)47110-4 Bayne, 1988, Structural analogs of human insulin-like growth factor I with reduced affinity for serum binding proteins and the type 2 insulin-like growth factor receptor, J Biol Chem, 263, 6233, 10.1016/S0021-9258(18)68777-0 Shooter, 1996, Insulin-like growth factor (IGF)-I A- and B-domain analogues with altered type 1 IGF and insulin receptor binding specificities, J Mol Endocrinol, 17, 237, 10.1677/jme.0.0170237 Hodgson, 1995, Mutations at positions 11 and 60 of insulin-like growth factor 1 reveal differences between its interactions with the type I insulin-like-growth-factor receptor and the insulin receptor, Eur J Biochem, 233, 299, 10.1111/j.1432-1033.1995.299_1.x Cascieri, 1988, Mutants of human insulin-like growth factor I with reduced affinity for the type 1 insulin-like growth factor receptor, Biochemistry, 27, 3229, 10.1021/bi00409a016 Bayne, 1990, The roles of tyrosines 24, 31, and 60 in the high affinity binding of insulin-like growth factor-I to the type 1 insulin-like growth factor receptor, J Biol Chem, 265, 15648, 10.1016/S0021-9258(18)55447-8 Magee, 1999, Insulin-like growth factor I and its binding proteins: a study of the binding interface using B-domain analogues, Biochemistry, 38, 15863, 10.1021/bi9910070 Jansson, 1998, The insulin-like growth factor (IGF)binding protein 1 binding epitope on IGF-I probed by heteronuclear NMR spectroscopy and mutational analysis, J Biol Chem, 273, 24701, 10.1074/jbc.273.38.24701 Jansson, 1997, Structural changes in insulin-like growth factor (IGF) I mutant proteins affecting binding kinetic rates to IGF binding protein 1 and IGF-I receptor, Biochemistry, 36, 4108, 10.1021/bi961553i Sakano, 1991, The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose 6-phosphate receptor or IGF-I receptor, J Biol Chem, 266, 20626, 10.1016/S0021-9258(18)54755-4 Roth, 1991, Mutants of human insulin-like growth factor II: expression and characterization of analogs with a substitution of TYR27 and/or a deletion of residues 62–67, Biochem Biophys Res Commun, 181, 907, 10.1016/0006-291X(91)91277-J Hashimoto, 1995, N-terminal deletion mutants of insulin-like growth factor-II (IGF-II) show Thr7 and Leu8 important for binding to insulin and IGF-I receptors and Leu8 critical for all IGF-II functions, J Biol Chem, 270, 18013, 10.1074/jbc.270.30.18013 Bagley, 1989, A key functional role for the insulin-like growth factor 1 N-terminal pentapeptide, Biochem J, 259, 665, 10.1042/bj2590665 Cara, 1990, An insulin-like growth factor I/insulin hybrid exhibiting high potency for interaction with the type I insulin-like growth factor and insulin receptors of placental plasma membranes, J Biol Chem, 265, 17820, 10.1016/S0021-9258(18)38237-1 Bayne, 1989, The C region of human insulin-like growth factor (IGF) I is required for high affinity binding to the type 1 IGF receptor, J Biol Chem, 264, 11004, 10.1016/S0021-9258(18)60418-1 Gill, 1996, Engineering the C-region of human insulin-like growth factor-1: implications for receptor binding, Protein Eng, 9, 1011, 10.1093/protein/9.11.1011 De Wolf, 1996, Solution structure of a mini IGF-1, Protein Sci, 5, 2193, 10.1002/pro.5560051106 Zhang, 1994, Positively charged side chains in the insulin-like growth factor-1 C- and D-regions determine receptor binding specificity, J Biol Chem, 269, 10609, 10.1016/S0021-9258(17)34103-0 Denley, 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, 10.1210/me.2004-0183 Kobayashi, 1986, Receptor binding and negative cooperativity of a mutant insulin, [LeuA3]-insulin, Biochem Biophys Res Commun, 137, 250, 10.1016/0006-291X(86)91203-9 Nanjo, 1987, Insulin Wakayama: familial mutant insulin syndrome in Japan, Diabetologia, 30, 87, 10.1007/BF00274577 Xu, 2004, Diabetes-associated mutations in insulin identify invariant receptor contacts, Diabetes, 53, 1599, 10.2337/diabetes.53.6.1599 Hua, 1991, Receptor binding redefined by a structural switch in a mutant human insulin, Nature, 354, 238, 10.1038/354238a0 Cascieri, 1989, Structural analogs of human insulin-like growth factor (IGF) I with altered affinity for type 2 IGF receptors, J Biol Chem, 264, 2199, 10.1016/S0021-9258(18)94162-1 Forbes, 2001, Contribution of residues A54 and L55 of the human insulin-like growth factor-II (IGF-II) A domain to Type 2 IGF receptor binding specificity, Growth Factors, 19, 163, 10.3109/08977190109001084 Schaffer, 1994, A model for insulin binding to the insulin receptor, Eur J Biochem, 221, 1127, 10.1111/j.1432-1033.1994.tb18833.x De Meyts, 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, S135, 10.1007/BF00400837 De Meyts, 2004, Insulin and its receptor: structure, function and evolution, Bioessays, 26, 1351, 10.1002/bies.20151 Xu, 2004, Diabetes-associated mutations in insulin: consecutive residues in the B chain contact distinct domains of the insulin receptor(,), Biochemistry, 43, 8356, 10.1021/bi0497796 Wan, 2004, Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues, Biochemistry, 43, 16119, 10.1021/bi048223f Huang, 2004, How insulin binds: the B-chain alpha-helix contacts the L1 beta-helix of the insulin receptor, J Mol Biol, 341, 529, 10.1016/j.jmb.2004.05.023 Hodgson, 1996, Involvement of phenylalanine 23 in the binding of IGF-1 to the insulin and type I IGF receptor, Regul Pept, 66, 191, 10.1016/S0167-0115(96)00102-4 Kristensen, 1995, A single-chain insulin-like growth factor I/insulin hybrid binds with high affinity to the insulin receptor, Biochem J, 305, 981, 10.1042/bj3050981 Sato, 1992, 1H-NMR assignment and secondary structure of human insulin-like growth factor-I (IGF-I) in solution, J Biochem (Tokyo), 111, 529, 10.1093/oxfordjournals.jbchem.a123791 Laajoki L, Milner S, Francis G, Carver J, Keniry M. BioMagResBank (http://www.bmrb.wisc.edu/) entry number 4278; 1998. Dubaquie, 2001, Binding protein-3-selective insulin-like growth factor I variants: engineering, biodistributions, and clearance, Endocrinology, 142, 165, 10.1210/en.142.1.165 Dubaquie, 1999, Total alanine-scanning mutagenesis of insulin-like growth factor I (IGF-I) identifies differential binding epitopes for IGFBP-1 and IGFBP-3, Biochemistry, 38, 6386, 10.1021/bi990089p Clemmons, 1992, Competition for binding to insulin-like growth factor (IGF) binding protein-2, 3, 4, and 5 by the IGFs and IGF analogs, Endocrinology, 131, 890, 10.1210/en.131.2.890 Bach, 1993, Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1–6, J Biol Chem, 268, 9246, 10.1016/S0021-9258(18)98342-0 Clemmons, 1990, Discrete alterations of the insulin-like growth factor I molecule which alter its affinity for insulin-like growth factor-binding proteins result in changes in bioactivity, J Biol Chem, 265, 12210, 10.1016/S0021-9258(19)38332-2 Moss, 1991, Insulin-like growth factor (IGF)-I and IGF-II binding to an IGF binding protein. An investigation using chemical modification of tyrosine residues as a structural probe for the sites of interaction, J Biol Chem, 266, 909, 10.1016/S0021-9258(17)35259-6 Kalus, 1998, Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions, EMBO J, 17, 6558, 10.1093/emboj/17.22.6558 Carrick FE, Hinds MG, McNeil KA, Wallace JC, Forbes BE, Norton RS. Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance. J Mol Endocrinol, in press. Oh, 1993, Characterization of the affinities of insulin-like growth factor (IGF)-binding proteins 1–4 for IGF-I, IGF-II, IGF-I/insulin hybrid, and IGF-I analogs, Endocrinol, 132, 1337, 10.1210/en.132.3.1337 Burgisser, 1991, Mutants of human insulin-like growth factor II with altered affinities for the type 1 and type 2 insulin-like growth factor receptor, J Biol Chem, 266, 1029, 10.1016/S0021-9258(17)35278-X Yandell, 1999, Kangaroo IGF-II is structurally and functionally similar to the human, J Endocrinol, 161, 445, 10.1677/joe.0.1610445 Blundell, 1978, Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding, Proc Natl Acad Sci USA, 75, 180, 10.1073/pnas.75.1.180 Pandini, 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, 10.1074/jbc.M202766200 King, 1992, Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins, J Mol Endocrinol, 8, 29, 10.1677/jme.0.0080029 Francis, 1992, Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency, J Mol Endocrinol, 8, 213, 10.1677/jme.0.0080213