Molecular Endocrinology, Vol 8, 40-50, Copyright © 1994 by Endocrine Society

ARTICLES

Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin- like growth factor-I (IGF-I) receptor in IGF-I action

H Kato, TN Faria, B Stannard, CT Roberts Jr and D LeRoith
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.

The insulin and insulin-like growth factor-I (IGF-I) receptors are related heterotetramers consisting of two extracellular ligand-binding alpha-subunits and two transmembrane beta-subunits whose cytoplasmic domains exhibit tyrosine kinase activity. Previous studies have shown that ATP binding by the cytoplasmic tyrosine kinase domains of these receptors is necessary to initiate the signal transduction pathway triggered by ligands or by ligand-mimetic antibodies, suggesting that receptor autophosphorylation is a necessary proximal step in this pathway. In the case of the insulin receptor, it has additionally been demonstrated that a cluster of three tyrosines in the kinase domain itself are the first to be phosphorylated, and that autophosphorylation of these particular residues is necessary for receptor activity. Using stably transfected NIH-3T3 cell lines, we now show that mutation of the analogous residues in the IGF-I receptor abolishes all short, intermediate, and long-term responses to IGF-I. These data suggest that the initial mechanisms of activation of the insulin and IGF-I receptors are very similar. Additionally, we have identified two parameters, induction of c-fos gene expression and ornithine decarboxylase enzyme activity, which are extremely sensitive to IGF-I stimulation and which will be particularly useful in evaluating the biological activity of other mutated versions of the IGF-I receptor.

This article has been cited by other articles:

				J. L. Holzman, L. Liu, B. J. Duke, A. E. Kemendy, and D. C. Eaton Transactivation of the IGF-1R by aldosterone Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1219 - F1228. [Abstract] [Full Text] [PDF]

				F. Giacco, G. Perruolo, E. D'Agostino, G. Fratellanza, E. Perna, S. Misso, G. Saldalamacchia, F. Oriente, F. Fiory, C. Miele, et al. Thrombin-activated platelets induce proliferation of human skin fibroblasts by stimulating autocrine production of insulin-like growth factor-1 FASEB J, November 1, 2006; 20(13): 2402 - 2404. [Abstract] [Full Text] [PDF]

				A. S. McCampbell, R. R. Broaddus, D. S. Loose, and P. J.A. Davies Overexpression of the Insulin-Like Growth Factor I Receptor and Activation of the AKT Pathway in Hyperplastic Endometrium. Clin. Cancer Res., November 1, 2006; 12(21): 6373 - 6378. [Abstract] [Full Text] [PDF]

				C. Blanquart, C. Gonzalez-Yanes, and T. Issad Monitoring the Activation State of Insulin/Insulin-Like Growth Factor-1 Hybrid Receptors Using Bioluminescence Resonance Energy Transfer Mol. Pharmacol., November 1, 2006; 70(5): 1802 - 1811. [Abstract] [Full Text] [PDF]

				W. Li and W. T. Miller Role of the Activation Loop Tyrosines in Regulation of the Insulin-like Growth Factor I Receptor-tyrosine Kinase J. Biol. Chem., August 18, 2006; 281(33): 23785 - 23791. [Abstract] [Full Text] [PDF]

				C. Blanquart, N. Boute, D. Lacasa, and T. Issad Monitoring the Activation State of the Insulin-Like Growth Factor-1 Receptor and Its Interaction with Protein Tyrosine Phosphatase 1B Using Bioluminescence Resonance Energy Transfer Mol. Pharmacol., September 1, 2005; 68(3): 885 - 894. [Abstract] [Full Text] [PDF]

				L. A. Maile and D. R. Clemmons The {alpha}V{beta}3 Integrin Regulates Insulin-Like Growth Factor I (IGF-I) Receptor Phosphorylation by Altering the Rate of Recruitment of the Src-Homology 2-Containing Phosphotyrosine Phosphatase-2 to the Activated IGF-I Receptor Endocrinology, November 1, 2002; 143(11): 4259 - 4264. [Abstract] [Full Text] [PDF]

				S. Munshi, M. Kornienko, D. L. Hall, J. C. Reid, L. Waxman, S. M. Stirdivant, P. L. Darke, and L. C. Kuo Crystal Structure of the Apo, Unactivated Insulin-like Growth Factor-1 Receptor Kinase. IMPLICATION FOR INHIBITOR SPECIFICITY J. Biol. Chem., October 4, 2002; 277(41): 38797 - 38802. [Abstract] [Full Text] [PDF]

				L. A. Maile and D. R. Clemmons Regulation of Insulin-like Growth Factor I Receptor Dephosphorylation by SHPS-1 and the Tyrosine Phosphatase SHP-2 J. Biol. Chem., March 8, 2002; 277(11): 8955 - 8960. [Abstract] [Full Text] [PDF]

				M. A. Guvakova, J. C. Adams, and D. Boettiger Functional role of {alpha}-actinin, PI 3-kinase and MEK1/2 in insulin-like growth factor I receptor kinase regulated motility of human breast carcinoma cells J. Cell Sci., January 11, 2002; 115(21): 4149 - 4165. [Abstract] [Full Text] [PDF]

				J. Dupont, J. Khan, B.-H. Qu, P. Metzler, L. Helman, and D. LeRoith Insulin and IGF-1 Induce Different Patterns of Gene Expression in Mouse Fibroblast NIH-3T3 Cells: Identification by cDNA Microarray Analysis Endocrinology, November 1, 2001; 142(11): 4969 - 4975. [Abstract] [Full Text] [PDF]

				L. Mauro, M. Bartucci, C. Morelli, S. Ando', and E. Surmacz IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1 J. Biol. Chem., October 19, 2001; 276(43): 39892 - 39897. [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]

				M. P. Playford, D. Bicknell, W. F. Bodmer, and V. M. Macaulay Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta -catenin PNAS, October 12, 2000; (2000) 210394297. [Abstract] [Full Text]

				P. Soni, M. Lakkis, M. N. Poy, M. A. Fernström, and S. M. Najjar The Differential Effects of pp120 (Ceacam 1) on the Mitogenic Action of Insulin and Insulin-Like Growth Factor 1 Are Regulated by the Nonconserved Tyrosine 1316 in the Insulin Receptor Mol. Cell. Biol., June 1, 2000; 20(11): 3896 - 3905. [Abstract] [Full Text]

				D. LeRoith Editorial: Insulin-Like Growth Factor I Receptor Signaling--Overlapping or Redundant Pathways? Endocrinology, April 1, 2000; 141(4): 1287 - 1288. [Full Text] [PDF]

				S. Walchli, M.-L. Curchod, R. P. Gobert, S. Arkinstall, and R. H. van Huijsduijnen Identification of Tyrosine Phosphatases That Dephosphorylate the Insulin Receptor. A BRUTE FORCE APPROACH BASED ON "SUBSTRATE-TRAPPING" MUTANTS J. Biol. Chem., March 24, 2000; 275(13): 9792 - 9796. [Abstract] [Full Text] [PDF]

				D. H. Schacher, R. W. VanHoy, Q. Liu, S. Arkins, R. Dantzer, G. G. Freund, and K. W. Kelley Developmental Expression of Insulin Receptor Substrate-2 During Dimethylsulfoxide-Induced Differentiation of Human HL-60 Cells J. Immunol., January 1, 2000; 164(1): 113 - 120. [Abstract] [Full Text] [PDF]

				K. Tajinda, J. Carroll, and C. T. Roberts Jr. Regulation of Insulin-Like Growth Factor I Receptor Promoter Activity by Wild-Type and Mutant Versions of the WT1 Tumor Suppressor Endocrinology, October 1, 1999; 140(10): 4713 - 4724. [Abstract] [Full Text]

				Y. Okubo, V. A. Blakesley, B. Stannard, S. Gutkind, and D. Le Roith Insulin-like Growth Factor-I Inhibits the Stress-activated Protein Kinase/c-Jun N-terminal Kinase J. Biol. Chem., October 2, 1998; 273(40): 25961 - 25966. [Abstract] [Full Text] [PDF]

				V. A. Blakesley, A. P. Koval, B. S. Stannard, A. Scrimgeour, and D. LeRoith Replacement of Tyrosine 1251 in the Carboxyl Terminus of the Insulin-like Growth Factor-I Receptor Disrupts the Actin Cytoskeleton and Inhibits Proliferation and Anchorage-independent Growth J. Biol. Chem., July 17, 1998; 273(29): 18411 - 18422. [Abstract] [Full Text] [PDF]

				S. M. Najjar, C. V. Choice, P. Soni, C. M. Whitman, and M. N. Poy Effect of pp120 on Receptor-mediated Insulin Endocytosis Is Regulated by the Juxtamembrane Domain of the Insulin Receptor J. Biol. Chem., May 22, 1998; 273(21): 12923 - 12928. [Abstract] [Full Text] [PDF]

				V. Baron, V. Calleja, P. Ferrari, F. Alengrin, and E. Van Obberghen p125Fak Focal Adhesion Kinase Is a Substrate for the Insulin and Insulin-like Growth Factor-I Tyrosine Kinase Receptors J. Biol. Chem., March 20, 1998; 273(12): 7162 - 7168. [Abstract] [Full Text] [PDF]

				I. Mothe, L. Delahaye, C. Filloux, S. Pons, M. F. White, and E. Van Obberghen Interaction of Wild Type and Dominant-Negative p55PIK Regulatory Subunit of Phosphatidylinositol 3-Kinase with Insulin-Like Growth Factor-1 Signaling Proteins Mol. Endocrinol., December 1, 1997; 11(13): 1911 - 1923. [Abstract] [Full Text] [PDF]

				R. Foncea, M. Andersson, A. Ketterman, V. Blakesley, M. Sapag-Hagar, P. H. Sugden, D. LeRoith, and S. Lavandero Insulin-like Growth Factor-I Rapidly Activates Multiple Signal Transduction Pathways in Cultured Rat Cardiac Myocytes J. Biol. Chem., August 1, 1997; 272(31): 19115 - 19124. [Abstract] [Full Text] [PDF]

				A. G. Scrimgeour, V. A. Blakesley, B. S. Stannard, and D. LeRoith Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways Are Not Sufficient for Insulin-Like Growth Factor I-Induced Mitogenesis and Tumorigenesis Endocrinology, June 1, 1997; 138(6): 2552 - 2558. [Abstract] [Full Text] [PDF]

				M. E. Cunningham, R. M. Stephens, D. R. Kaplan, and L. A. Greene Autophosphorylation of Activation Loop Tyrosines Regulates Signaling by the TRK Nerve Growth Factor Receptor J. Biol. Chem., April 18, 1997; 272(16): 10957 - 10967. [Abstract] [Full Text] [PDF]

				J. E. Peterson, G. Kulik, T. Jelinek, C. W.M. Reuter, J. A. Shannon, and M. J. Weber Src Phosphorylates the Insulin-like Growth Factor Type I Receptor on the Autophosphorylation Sites. REQUIREMENT FOR TRANSFORMATION BY src J. Biol. Chem., December 6, 1996; 271(49): 31562 - 31571. [Abstract] [Full Text] [PDF]

				R. J. Urban, M. Nagamani, and Y. Bodenburg Tumor Necrosis Factor alpha Inhibits Transcriptional Activity of the Porcine P-45011A Insulin-like Growth Factor Response Element J. Biol. Chem., December 6, 1996; 271(49): 31699 - 31703. [Abstract] [Full Text] [PDF]

				C. Hernández-Sánchez, V. Blakesley, T. Kalebic, L. Helman, and D. LeRoith The Role of the Tyrosine Kinase Domain of the Insulin-like Growth Factor-I Receptor in Intracellular Signaling, Cellular Proliferation, and Tumorigenesis J. Biol. Chem., December 8, 1995; 270(49): 29176 - 29181. [Abstract] [Full Text] [PDF]

				S. Tartare-Deckert, D. Sawka-Verhelle, J. Murdaca, and E. Van Obberghen Evidence for a Differential Interaction of SHC and the Insulin Receptor Substrate-1 (IRS-1) with the Insulin-like Growth Factor-I (IGF-I) Receptor in the Yeast Two-hybrid System J. Biol. Chem., October 6, 1995; 270(40): 23456 - 23460. [Abstract] [Full Text] [PDF]

				M. Miura, E. Surmacz, J.-L. Burgaud, and R. Baserga Different Effects on Mitogenesis and Transformation of a Mutation at Tyrosine 1251 of the Insulin-like Growth Factor I Receptor J. Biol. Chem., September 22, 1995; 270(38): 22639 - 22644. [Abstract] [Full Text] [PDF]

				K. Takahashi, K. Yonezawa, and I. Nishimoto Insulin-like Growth Factor I Receptor Activated by a Transmembrane Mutation J. Biol. Chem., August 11, 1995; 270(32): 19041 - 19045. [Abstract] [Full Text] [PDF]

				B. L. Seely, D. R. Reichart, P. A. Staubs, B. H. Jhun, D. Hsu, H. Maegawa, K. L. Milarski, A. R. Saltiel, and J. M. Olefsky Localization of the Insulin-like Growth Factor I Receptor Binding Sites for the SH2 Domain Proteins p85, Syp, and GTPase Activating Protein J. Biol. Chem., August 11, 1995; 270(32): 19151 - 19157. [Abstract] [Full Text] [PDF]

				V. A. Blakesley, H. Kato, C. T. Roberts Jr., and D. LeRoith Mutation of a Conserved Amino Acid Residue (Tryptophan 1173) in the Tyrosine Kinase Domain of the IGF-I Receptor Abolishes Autophosphorylation but Does Not Eliminate Biologic Function J. Biol. Chem., February 10, 1995; 270(6): 2764 - 2769. [Abstract] [Full Text] [PDF]

				A. Yam, T. Hyun, and W. Li Characterization of Insulin-like Growth Factor I (IGF-I) Receptor Mutants for Their Effects on IGF-I- and Interleukin 4-mediated DNA Synthesis of 32D Cells J. Biol. Chem., June 22, 2001; 276(26): 24409 - 24413. [Abstract] [Full Text] [PDF]

				P. Brodt, L. Fallavollita, A.-M. Khatib, A. A. Samani, and D. Zhang Cooperative Regulation of the Invasive and Metastatic Phenotypes by Different Domains of the Type I Insulin-like Growth Factor Receptor beta Subunit J. Biol. Chem., August 31, 2001; 276(36): 33608 - 33615. [Abstract] [Full Text] [PDF]

				M. P. Playford, D. Bicknell, W. F. Bodmer, and V. M. Macaulay Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta -catenin PNAS, October 24, 2000; 97(22): 12103 - 12108. [Abstract] [Full Text] [PDF]