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The Insulin-Like Growth Factor-Binding Protein (IGFBP) Superfamily¹

Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon 97201

I. Introduction

A. Concept of an IGFBP superfamily

B. Superfamily nomenclature

II. IGFBP Family

A. Structure of IGFBPs

B. Correlations between structure and function

C. Biological functions of IGFBPs

D. Genomics of IGFBPs

III. Mac25

A. IGFBP-rP1 (Mac25/TAF/PSF)

IV. CCN Family

A. IGFBP-rP2 (CTGF)

B. IGFBP-rP3 (NovH)

C. IGFBP-rP4 (Cyr61)

D. New members

V. L56

A. IGFBP-rP5 (L56/HtrA)

VI. ESM-1

A. IGFBP-rP6 (endothelial specific molecule-1)

VII. Structural Relationships Within the IGFBP Superfamily

A. Protein domains (modules)

B. Gene structure and correlation with protein domains

VIII. Functional Relationships Within the IGFBP Superfamily

A. IGF binding

B. Insulin binding

C. IGF/insulin-independent actions

IX. Evolutionary Relationships Within the IGFBP Superfamily

A. N-terminal domains

B. C-terminal domains

C. Evolutionary models

X. Summary

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				I. Y. C. Sun, M. T. Overgaard, C. Oxvig, and L. C. Giudice Pregnancy-Associated Plasma Protein A Proteolytic Activity Is Associated with the Human Placental Trophoblast Cell Membrane J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5235 - 5240. [Abstract] [Full Text] [PDF]

				R. D. Devlin, Z. Du, V. Buccilli, V. Jorgetti, and E. Canalis Transgenic Mice Overexpressing Insulin-Like Growth Factor Binding Protein-5 Display Transiently Decreased Osteoblastic Function and Osteopenia Endocrinology, October 1, 2002; 143(10): 3955 - 3962. [Abstract] [Full Text] [PDF]

				A. Bachelot, P. Monget, P. Imbert-Bollore, K. Coshigano, J. J. Kopchick, P. A. Kelly, and N. Binart Growth Hormone Is Required for Ovarian Follicular Growth Endocrinology, October 1, 2002; 143(10): 4104 - 4112. [Abstract] [Full Text] [PDF]

				E. J. Kim, P. E. Holthuizen, H. S. Park, Y. L. Ha, K. C. Jung, and J. H. Y. Park Trans-10,cis-12-conjugated linoleic acid inhibits Caco-2 colon cancer cell growth Am J Physiol Gastrointest Liver Physiol, August 1, 2002; 283(2): G357 - G367. [Abstract] [Full Text] [PDF]

				T. J. Maures and C. Duan Structure, Developmental Expression, and Physiological Regulation of Zebrafish IGF Binding Protein-1 Endocrinology, July 1, 2002; 143(7): 2722 - 2731. [Abstract] [Full Text] [PDF]

				H.-M. P. Wilson, R. S. Birnbaum, M. Poot, L. S. Quinn, and K. Swisshelm Insulin-like Growth Factor Binding Protein-related Protein 1 Inhibits Proliferation of MCF-7 Breast Cancer Cells via a Senescence-like Mechanism Cell Growth Differ., May 1, 2002; 13(5): 205 - 213. [Abstract] [Full Text] [PDF]

				A. Hourvitz, A. Kuwahara, J. D. Hennebold, A. B. Tavares, H. Negishi, T. H. Lee, G. F. Erickson, and E. Y. Adashi The Regulated Expression of the Pregnancy-Associated Plasma Protein-A in the Rodent Ovary: A Proposed Role in the Development of Dominant Follicles and of Corpora Lutea Endocrinology, May 1, 2002; 143(5): 1833 - 1844. [Abstract] [Full Text] [PDF]

				J. Liu, V.-M. Kosma, T. Vanttinen, C. Hyden-Granskog, and R. Voutilainen Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa-luteal cells Mol. Hum. Reprod., February 1, 2002; 8(2): 136 - 141. [Abstract] [Full Text] [PDF]

				P Vorwerk, H Wex, B Hohmann, K Mohnike, U Schmidt, and U Mittler Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia Mol. Pathol., February 1, 2002; 55(1): 40 - 45. [Abstract] [Full Text] [PDF]

				C. H. Lang, G. J. Nystrom, and R. A. Frost Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R207 - R215. [Abstract] [Full Text] [PDF]

				Y. Lu, X. Zi, Y. Zhao, D. Mascarenhas, and M. Pollak Insulin-Like Growth Factor-I Receptor Signaling and Resistance to Trastuzumab (Herceptin) J Natl Cancer Inst, December 19, 2001; 93(24): 1852 - 1857. [Abstract] [Full Text] [PDF]

				J. Nakae, Y. Kido, and D. Accili Distinct and Overlapping Functions of Insulin and IGF-I Receptors Endocr. Rev., December 1, 2001; 22(6): 818 - 835. [Abstract] [Full Text] [PDF]

				A. Hoeflich, R. Reisinger, H. Lahm, W. Kiess, W. F. Blum, H. J. Kolb, M. M. Weber, and E. Wolf Insulin-like Growth Factor-binding Protein 2 in Tumorigenesis: Protector or Promoter? Cancer Res., December 1, 2001; 61(24): 8601 - 8610. [Full Text] [PDF]

				C. G. Goodyer, R. M. O. Figueiredo, S. Krackovitch, L. De Souza Li, J. A. Manalo, and G. Zogopoulos Characterization of the growth hormone receptor in human dermal fibroblasts and liver during development Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1213 - E1220. [Abstract] [Full Text] [PDF]

				A. Decensi, H. Johansson, R. Miceli, L. Mariani, T. Camerini, E. Cavadini, M. G. Di Mauro, A. Barreca, A. G. Gonzaga, S. Diani, et al. Long-Term Effects of Fenretinide, a Retinoic Acid Derivative, on the Insulin-like Growth Factor System in Women with Early Breast Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2001; 10(10): 1047 - 1053. [Abstract] [Full Text] [PDF]

				M. W. Elmlinger, I. Mayer, D. Schnabel, B. S. Schuett, D. Diesing, G. Romalo, H. A. Wollmann, W. Weidemann, K.-D. Spindler, M. B. Ranke, et al. Decreased Expression of IGF-II and Its Binding Protein, IGF-Binding Protein-2, in Genital Skin Fibroblasts of Patients with Complete Androgen Insensitivity Syndrome Compared with Normally Virilized Males J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4741 - 4746. [Abstract] [Full Text] [PDF]

				C. K. Buckway, E. M. Wilson, M. Ahlsen, P. Bang, Y. Oh, and R. G. Rosenfeld Mutation of Three Critical Amino Acids of the N-Terminal Domain of IGF-Binding Protein-3 Essential for High Affinity IGF Binding J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4943 - 4950. [Abstract] [Full Text] [PDF]

				Z Laron Insulin-like growth factor 1 (IGF-1): a growth hormone Mol. Pathol., October 1, 2001; 54(5): 311 - 316. [Abstract] [Full Text] [PDF]

				P Vilmos, K Gaudenz, Z Hegedus, and J L Marsh The Twisted gastrulation family of proteins, together with the IGFBP and CCN families, comprise the TIC superfamily of cysteine rich secreted factors Mol. Pathol., October 1, 2001; 54(5): 317 - 323. [Abstract] [Full Text] [PDF]

				E. M. Wilson, Y. Oh, V. Hwa, and R. G. Rosenfeld Interaction of IGF-Binding Protein-Related Protein 1 with a Novel Protein, Neuroendocrine Differentiation Factor, Results in Neuroendocrine Differentiation of Prostate Cancer Cells J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4504 - 4511. [Abstract] [Full Text] [PDF]

				T. C. Voss, M. P. Flynn, and D. L. Hurley IGF-I Causes an Ultrasensitive Reduction in GH mRNA Levels via an Extracellular Mechanism Involving IGF Binding Proteins Mol. Endocrinol., September 1, 2001; 15(9): 1549 - 1558. [Abstract] [Full Text] [PDF]

				C. Martinerie, C. Gicquel, A. Louvel, M. Laurent, P. N. Schofield, and Y. Le Bouc Altered Expression of novH Is Associated with Human Adrenocortical Tumorigenesis J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3929 - 3940. [Abstract] [Full Text] [PDF]

				T. Nickerson, F. Chang, D. Lorimer, S. P. Smeekens, C. L. Sawyers, and M. Pollak In Vivo Progression of LAPC-9 and LNCaP Prostate Cancer Models to Androgen Independence Is Associated with Increased Expression of Insulin-like Growth Factor I (IGF-I) and IGF-I Receptor (IGF-IR) Cancer Res., August 1, 2001; 61(16): 6276 - 6280. [Abstract] [Full Text] [PDF]

				K. Prelle, M. Stojkovic, K. Boxhammer, J. Motlik, D. Ewald, G. J. Arnold, and E. Wolf Insulin-Like Growth Factor I (IGF-I) and Long R3IGF-I Differently Affect Development and Messenger Ribonucleic Acid Abundance for IGF-Binding Proteins and Type I IGF Receptors in in Vitro Produced Bovine Embryos Endocrinology, March 1, 2001; 142(3): 1309 - 1316. [Abstract] [Full Text] [PDF]

				R. G. Rosenfeld, V. Hwa, and Y. Oh Nomenclature of the Insulin-Like Growth Factor-Binding Protein Superfamily J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 946 - 946. [Full Text]