This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, W. Articles by Keller, G.-A. Search for Related Content PubMed PubMed Citation Articles by Li, W. Articles by Keller, G.-A.

Nuclear Transport of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 in Opossum Kidney Cells

Department of Pharmacokinetics and Metabolism (W.L., H.R.W., P.J.F., G.-A.K.), Genentech, Inc., South San Francisco, California 94080; and Department of Medicine (J.F., R.R.), Stanford University and Veteran Affairs Medical Center, Palo Alto, California 94304

Address all correspondence and requests for reprints to: Dr. Gilbert-André Keller, Genentech, Inc., 460 Point San Bruna Boulevard, South San Francisco, California 94080.

When added to cultured opossum kidney cells, IGF-I is internalized and transported to distinct intracellular compartments that depend on the cell location within the monolayer. In resting cells away from the periphery of the monolayer, IGF-I is internalized by a clathrin coated pit pathway and delivered to the endosomal compartment. In contrast, cells growing at the edges of a monolayer or an experimental wound internalize IGF-I by an alternative route which rapidly delivers IGF-I to the nucleus. Similarly to IGF-I, IGFBP-3 is also internalized and accumulates in the endosomal compartment in resting cells whereas it is targeted to the nucleus in proliferating cells. IGFBP-3, which contains a putative nuclear targeting signal, may act as a carrier for IGF-I nuclear transport. The transport of IGF-I and IGFBP-3 to two different compartments may influence their biological activity.

This article has been cited by other articles:

				S. Jogie-Brahim, D. Feldman, and Y. Oh Unraveling Insulin-Like Growth Factor Binding Protein-3 Actions in Human Disease Endocr. Rev., August 1, 2009; 30(5): 417 - 437. [Abstract] [Full Text] [PDF]

				P. M. Yamada and K.-W. Lee Perspectives in mammalian IGFBP-3 biology: local vs. systemic action Am J Physiol Cell Physiol, May 1, 2009; 296(5): C954 - C976. [Abstract] [Full Text] [PDF]

				S. S. Y. Chan, L. J. Schedlich, S. M. Twigg, and R. C. Baxter Inhibition of adipocyte differentiation by insulin-like growth factor-binding protein-3 Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E654 - E663. [Abstract] [Full Text] [PDF]

				I. Villalpando, E. Lira, G. Medina, E. Garcia-Garcia, and O. Echeverria Insulin-Like Growth Factor 1 Is Expressed in Mouse Developing Testis and Regulates Somatic Cell Proliferation Experimental Biology and Medicine, April 1, 2008; 233(4): 419 - 426. [Abstract] [Full Text] [PDF]

				G. Zappala, C. Elbi, J. Edwards, J. Gorenstein, M. M. Rechler, and N. Bhattacharyya Induction of Apoptosis in Human Prostate Cancer Cells by Insulin-Like Growth Factor Binding Protein-3 Does Not Require Binding to Retinoid X Receptor-{alpha} Endocrinology, April 1, 2008; 149(4): 1802 - 1812. [Abstract] [Full Text] [PDF]

				W. R. Dayton and M. E. White Cellular and molecular regulation of muscle growth and development in meat animals J Anim Sci, April 1, 2008; 86(14_suppl): E217 - E225. [Abstract] [Full Text] [PDF]

				L. J. Schedlich, A. Muthukaruppan, M. K. O'Han, and R. C. Baxter Insulin-Like Growth Factor Binding Protein-5 Interacts with the Vitamin D Receptor and Modulates the Vitamin D Response in Osteoblasts Mol. Endocrinol., October 1, 2007; 21(10): 2378 - 2390. [Abstract] [Full Text] [PDF]

				L. J. Cobb, B. Liu, K.-W. Lee, and P. Cohen Phosphorylation by DNA-Dependent Protein Kinase Is Critical for Apoptosis Induction by Insulin-Like Growth Factor Binding Protein-3. Cancer Res., November 15, 2006; 66(22): 10878 - 10884. [Abstract] [Full Text] [PDF]

				N. Bhattacharyya, K. Pechhold, H. Shahjee, G. Zappala, C. Elbi, B. Raaka, M. Wiench, J. Hong, and M. M. Rechler Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus J. Biol. Chem., August 25, 2006; 281(34): 24588 - 24601. [Abstract] [Full Text] [PDF]

				M. Oufattole, S. W.-J. Lin, B. Liu, D. Mascarenhas, P. Cohen, and B. D. Rodgers Ribonucleic Acid Polymerase II Binding Subunit 3 (Rpb3), a Potential Nuclear Target of Insulin-Like Growth Factor Binding Protein-3 Endocrinology, May 1, 2006; 147(5): 2138 - 2146. [Abstract] [Full Text] [PDF]

				F. R. Santer, N. Bacher, B. Moser, D. Morandell, S. Ressler, S. M. Firth, G. A. Spoden, C. Sergi, R. C. Baxter, P. Jansen-Durr, et al. Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysis. Cancer Res., March 15, 2006; 66(6): 3024 - 3033. [Abstract] [Full Text] [PDF]

				J. V. Silha, Y. Gui, S. Mishra, A. Leckstrom, P. Cohen, and L. J. Murphy Overexpression of Gly56/Gly80/Gly81-Mutant Insulin-Like Growth Factor-Binding Protein-3 in Transgenic Mice Endocrinology, March 1, 2005; 146(3): 1523 - 1531. [Abstract] [Full Text] [PDF]

				Y. Li, J. Xiang, and C. Duan Insulin-like Growth Factor-binding Protein-3 Plays an Important Role in Regulating Pharyngeal Skeleton and Inner Ear Formation and Differentiation J. Biol. Chem., February 4, 2005; 280(5): 3613 - 3620. [Abstract] [Full Text] [PDF]

				H. Gronbaek, A. Flyvbjerg, L. Mellemkjaer, A. Tjonneland, J. Christensen, H. Toft Sorensen, and K. Overvad Serum Insulin-Like Growth Factors, Insulin-Like Growth Factor Binding Proteins, and Breast Cancer Risk in Postmenopausal Women Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1759 - 1764. [Abstract] [Full Text] [PDF]

				J. F. Kuemmerle, K. S. Murthy, and J. G. Bowers IGFBP-3 activates TGF-{beta} receptors and directly inhibits growth in human intestinal smooth muscle cells Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G795 - G802. [Abstract] [Full Text] [PDF]

				E. M. Ongeri, Q. Zhu, M. F. Verderame, and J. M. Hammond Insulin-Like Growth Factor-Binding Protein-3 in Porcine Ovarian Granulosa Cells: Gene Cloning, Promoter Mapping, and Follicle-Stimulating Hormone Regulation Endocrinology, April 1, 2004; 145(4): 1776 - 1785. [Abstract] [Full Text] [PDF]

				Q. Xu, S. Li, Y. Zhao, T. J. Maures, P. Yin, and C. Duan Evidence That IGF Binding Protein-5 Functions as a Ligand-Independent Transcriptional Regulator in Vascular Smooth Muscle Cells Circ. Res., March 19, 2004; 94(5): e46 - e54. [Abstract] [Full Text] [PDF]

				K.-W. Lee, B. Liu, L. Ma, H. Li, P. Bang, H. P. Koeffler, and P. Cohen Cellular Internalization of Insulin-like Growth Factor Binding Protein-3: DISTINCT ENDOCYTIC PATHWAYS FACILITATE RE-UPTAKE AND NUCLEAR LOCALIZATION J. Biol. Chem., January 2, 2004; 279(1): 469 - 476. [Abstract] [Full Text] [PDF]

				S. R. Edmondson, S. P. Thumiger, G. A. Werther, and C. J. Wraight Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems Endocr. Rev., December 1, 2003; 24(6): 737 - 764. [Abstract] [Full Text] [PDF]

				L. J. Schedlich, T. Nilsen, A. P. John, D. A. Jans, and R. C. Baxter Phosphorylation of Insulin-Like Growth Factor Binding Protein-3 by Deoxyribonucleic Acid-Dependent Protein Kinase Reduces Ligand Binding and Enhances Nuclear Accumulation Endocrinology, May 1, 2003; 144(5): 1984 - 1993. [Abstract] [Full Text] [PDF]

				S. M. Firth and R. C. Baxter Cellular Actions of the Insulin-Like Growth Factor Binding Proteins Endocr. Rev., December 1, 2002; 23(6): 824 - 854. [Abstract] [Full Text] [PDF]

				R. J. Wright, J. M.P. Holly, R. Galea, M. Brincat, and H. D. Mason Insulin-Like Growth Factor (IGF)-Independent Effects of IGF Binding Protein-4 on Human Granulosa Cell Steroidogenesis Biol Reprod, September 1, 2002; 67(3): 776 - 781. [Abstract] [Full Text] [PDF]

				S. Ross, S. D. Spencer, I. Holcomb, C. Tan, J. Hongo, B. Devaux, L. Rangell, G. A. Keller, P. Schow, R. M. Steeves, et al. Prostate Stem Cell Antigen as Therapy Target: Tissue Expression and in Vivo Efficacy of an Immunoconjugate Cancer Res., May 1, 2002; 62(9): 2546 - 2553. [Abstract] [Full Text] [PDF]

				J. Hong, G. Zhang, F. Dong, and M. M. Rechler Insulin-like Growth Factor (IGF)-binding Protein-3 Mutants That Do Not Bind IGF-I or IGF-II Stimulate Apoptosis in Human Prostate Cancer Cells J. Biol. Chem., March 15, 2002; 277(12): 10489 - 10497. [Abstract] [Full Text] [PDF]

				B. A. Booth, M. Boes, B. L. Dake, K. L. Knudtson, and R. S. Bar IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E52 - E58. [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]

				R C Baxter Signalling pathways involved in antiproliferative effects of IGFBP-3: a review Mol. Pathol., June 1, 2001; 54(3): 145 - 148. [Abstract] [Full Text]

				B. Mannhardt, S. A. Weinzimer, M. Wagner, M. Fiedler, P. Cohen, P. Jansen-Dürr, and W. Zwerschke Human Papillomavirus Type 16 E7 Oncoprotein Binds and Inactivates Growth-Inhibitory Insulin-Like Growth Factor Binding Protein 3 Mol. Cell. Biol., September 1, 2000; 20(17): 6483 - 6495. [Abstract] [Full Text]

				R. C. Baxter Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E967 - E976. [Abstract] [Full Text] [PDF]

				J. A. Coverley, J. L. Martin, and R. C. Baxter The Effect of Phosphorylation by Casein Kinase 2 on the Activity of Insulin-Like Growth Factor-Binding Protein-3 Endocrinology, February 1, 2000; 141(2): 564 - 570. [Abstract] [Full Text] [PDF]

				W Li and G Keller VEGF nuclear accumulation correlates with phenotypical changes in endothelial cells J. Cell Sci., January 5, 2000; 113(9): 1525 - 1534. [Abstract] [PDF]

				V. Hwa, Y. Oh, and R. G. Rosenfeld The Insulin-Like Growth Factor-Binding Protein (IGFBP) Superfamily Endocr. Rev., December 1, 1999; 20(6): 761 - 787. [Abstract] [Full Text]

				Y. Shang, C. R. Baumrucker, and M. H. Green Signal Relay by Retinoic Acid Receptors alpha  and beta  in the Retinoic Acid-induced Expression of Insulin-like Growth Factor-binding Protein-3 in Breast Cancer Cells J. Biol. Chem., June 18, 1999; 274(25): 18005 - 18010. [Abstract] [Full Text] [PDF]

				L. J. Schedlich, T. F. Young, S. M. Firth, and R. C. Baxter Insulin-like Growth Factor-binding Protein (IGFBP)-3 and IGFBP-5 Share a Common Nuclear Transport Pathway in T47D Human Breast Carcinoma Cells J. Biol. Chem., July 17, 1998; 273(29): 18347 - 18352. [Abstract] [Full Text] [PDF]

				E. Nabeyrat, V. Besnard, S. Corroyer, V. Cazals, and A. Clement Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system Am J Physiol Lung Cell Mol Physiol, July 1, 1998; 275(1): L71 - L79. [Abstract] [Full Text] [PDF]

				K. Chan and E. M. Spencer Megakaryocytes Endocytose Insulin-Like Growth Factor (IGF) I and IGF-Binding Protein-3: A Novel Mechanism Directing Them into {alpha} Granules of Platelets Endocrinology, February 1, 1998; 139(2): 559 - 565. [Abstract] [Full Text] [PDF]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]

				L. J. Schedlich, S. L. Le Page, S. M. Firth, L. J. Briggs, D. A. Jans, and R. C. Baxter Nuclear Import of Insulin-like Growth Factor-binding Protein-3 and -5 Is Mediated by the Importin beta Subunit J. Biol. Chem., July 28, 2000; 275(31): 23462 - 23470. [Abstract] [Full Text] [PDF]

				B. Liu, H.-Y. Lee, S. A. Weinzimer, D. R. Powell, J. L. Clifford, J. M. Kurie, and P. Cohen Direct Functional Interactions between Insulin-like Growth Factor-binding Protein-3 and Retinoid X Receptor-alpha Regulate Transcriptional Signaling and Apoptosis J. Biol. Chem., October 20, 2000; 275(43): 33607 - 33613. [Abstract] [Full Text] [PDF]