HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 18, 14588-14596, May 4, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/18/14588    most recent M008866200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Esparza-López, J. Articles by López-Casillas, F. Search for Related Content PubMed PubMed Citation Articles by Esparza-López, J. Articles by López-Casillas, F. Social Bookmarking                      What's this?

Ligand Binding and Functional Properties of Betaglycan, a Co-receptor of the Transforming Growth Factor- Superfamily
SPECIALIZED BINDING REGIONS FOR TRANSFORMING GROWTH FACTOR- AND INHIBIN A^*

José Esparza-López, José Luis Montiel, M. Magdalena Vilchis-Landeros, Toshihide Okadome^§, Kohei Miyazono^§, and Fernando López-Casillas^¶

From the  Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, UNAM Apartado Postal 70-246, México City, D. F., 04510, México and ^§ The Cancer Institute, Tokyo, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan

Betaglycan, also known as the transforming growth factor- (TGF-) type III receptor, is a membrane-anchored proteoglycan that binds TGF- via its core protein. Deletion mutagenesis analysis has revealed two regions of betaglycan ectodomain capable of binding TGF-: one at the amino-terminal half, the endoglin-related region (López-Casillas, F., Payne, H., Andres, J. L., and Massagué, J. (1994) J. Cell Biol. 124, 557-568), and the other at the carboxyl-terminal half, the uromodulin-related region (Pepin, M.-C., Beauchemin, M., Plamondon, J., and O'Connor-McCourt, M. D. (1994) Proc. Natl. Acad. Sci. U. S. A 91, 6997-7001). In the present work we have functionally characterized these ligand binding regions. Similar to the wild type receptor, both regions bind TGF-2 with higher affinity than TGF-1. However, only the endoglin-related region increases the TGF-2 labeling of the TGF- type II receptor, the so-called "TGF- -presentation" function of the wild type receptor. Despite this preference, both regions as well as the wild type receptor mediate the TGF-2-dependent Smad2 phosphorylation, indicating that they can function indistinguishably as TGF--enhancing co-receptors. On the other hand, we found that the recently described ability of the wild type betaglycan to bind inhibin A is a property of the core protein that resides in the uromodulin-related region. Binding competition experiments indicate that this region binds inhibin and TGF- with the following relative affinities: TGF-2 > inhibin A > TGF-1. All together, the present results suggest that betaglycan ectodomain is endowed with two bona fide independent ligand binding domains that can perform specialized functions as co-receptors of distinct members of the TGF- superfamily.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. C. Finger, N. Y. Lee, H.-j. You, and G. C. Blobe Endocytosis of the Type III Transforming Growth Factor-{beta} (TGF-{beta}) Receptor through the Clathrin-independent/Lipid Raft Pathway Regulates TGF-{beta} Signaling and Receptor Down-regulation J. Biol. Chem., December 12, 2008; 283(50): 34808 - 34818. [Abstract] [Full Text] [PDF]

				E. V. Verona, Y. Tang, T. K. Millstead, A. P. Hinck, J. K. Agyin, and L.-Z. Sun Expression, purification and characterization of BGERII: a novel pan-TGF{beta} inhibitor Protein Eng. Des. Sel., July 1, 2008; 21(7): 463 - 473. [Abstract] [Full Text] [PDF]

				I. Imhof, W. J. Gasper, and R. Derynck Association of tetraspanin CD9 with transmembrane TGF{alpha} confers alterations in cell-surface presentation of TGF{alpha} and cytoskeletal organization J. Cell Sci., July 1, 2008; 121(13): 2265 - 2274. [Abstract] [Full Text] [PDF]

				Y. Makanji, K. L. Walton, M. C. Wilce, K. L. Chan, D. M. Robertson, and C. A. Harrison Suppression of Inhibin A Biological Activity by Alterations in the Binding Site for Betaglycan J. Biol. Chem., June 13, 2008; 283(24): 16743 - 16751. [Abstract] [Full Text] [PDF]

				K. C. Kirkbride, T. A. Townsend, M. W. Bruinsma, J. V. Barnett, and G. C. Blobe Bone Morphogenetic Proteins Signal through the Transforming Growth Factor-{beta} Type III Receptor J. Biol. Chem., March 21, 2008; 283(12): 7628 - 7637. [Abstract] [Full Text] [PDF]

				H. J. You, M. W. Bruinsma, T. How, J. H. Ostrander, and G. C. Blobe The type III TGF- receptor signals through both Smad3 and the p38 MAP kinase pathways to contribute to inhibition of cell proliferation Carcinogenesis, December 1, 2007; 28(12): 2491 - 2500. [Abstract] [Full Text] [PDF]

				P. G. Farnworth, Y. Wang, R. Escalona, P. Leembruggen, G. T. Ooi, and J. K. Findlay Transforming Growth Factor-{beta} Blocks Inhibin Binding to Different Target Cell Types in a Context-Dependent Manner through Dual Mechanisms Involving Betaglycan Endocrinology, November 1, 2007; 148(11): 5355 - 5368. [Abstract] [Full Text] [PDF]

				S J. Lin, T. F Lerch, R. W Cook, T. S Jardetzky, and T. K Woodruff The structural basis of TGF-{beta}, bone morphogenetic protein, and activin ligand binding. Reproduction, August 1, 2006; 132(2): 179 - 190. [Abstract] [Full Text] [PDF]

				E. Wiater, C. A. Harrison, K. A. Lewis, P. C. Gray, and W. W. Vale Identification of Distinct Inhibin and Transforming Growth Factor beta-binding Sites on Betaglycan: FUNCTIONAL SEPARATION OF BETAGLYCAN CO-RECEPTOR ACTIONS J. Biol. Chem., June 23, 2006; 281(25): 17011 - 17022. [Abstract] [Full Text] [PDF]

				H. Dixit, M. Deendayal, and L. Singh Mutational analysis of the mature peptide region of inhibin genes in Indian women with ovarian failure Hum. Reprod., August 1, 2004; 19(8): 1760 - 1764. [Abstract] [Full Text] [PDF]

				G. De Crescenzo, P. L. Pham, Y. Durocher, H. Chao, and M. D. O'Connor-McCourt Enhancement of the Antagonistic Potency of Transforming Growth Factor-{beta} Receptor Extracellular Domains by Coiled Coil-induced Homo- and Heterodimerization J. Biol. Chem., June 18, 2004; 279(25): 26013 - 26018. [Abstract] [Full Text] [PDF]

				G. Velasco-Loyden, J. Arribas, and F. Lopez-Casillas The Shedding of Betaglycan Is Regulated by Pervanadate and Mediated by Membrane Type Matrix Metalloprotease-1 J. Biol. Chem., February 27, 2004; 279(9): 7721 - 7733. [Abstract] [Full Text] [PDF]

				S. C. Chapman and T. K. Woodruff Betaglycan Localization in the Female Rat Pituitary: Implications for the Regulation of Follicle-Stimulating Hormone by Inhibin Endocrinology, December 1, 2003; 144(12): 5640 - 5649. [Abstract] [Full Text] [PDF]

				J. Liu, T. Kuulasmaa, V.-M. Kosma, R. Butzow, T. Vanttinen, C. Hyden-Granskog, and R. Voutilainen Expression of Betaglycan, an Inhibin Coreceptor, in Normal Human Ovaries and Ovarian Sex Cord-Stromal Tumors and Its Regulation in Cultured Human Granulosa-Luteal Cells J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5002 - 5008. [Abstract] [Full Text] [PDF]

				K. L. Stenvers, M. L. Tursky, K. W. Harder, N. Kountouri, S. Amatayakul-Chantler, D. Grail, C. Small, R. A. Weinberg, A. M. Sizeland, and H.-J. Zhu Heart and Liver Defects and Reduced Transforming Growth Factor {beta}2 Sensitivity in Transforming Growth Factor {beta} Type III Receptor-Deficient Embryos Mol. Cell. Biol., June 15, 2003; 23(12): 4371 - 4385. [Abstract] [Full Text] [PDF]

				G. Chen, G. Grotendorst, T. Eichholtz, and N. Khalil GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-beta receptors Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L548 - L556. [Abstract] [Full Text] [PDF]

				F. Lopez-Casillas, C. Riquelme, Y. Perez-Kato, M. V. Ponce-Castaneda, N. Osses, J. Esparza-Lopez, G. Gonzalez-Nunez, C. Cabello-Verrugio, V. Mendoza, V. Troncoso, et al. Betaglycan Expression Is Transcriptionally Up-regulated during Skeletal Muscle Differentiation. CLONING OF MURINE BETAGLYCAN GENE PROMOTER AND ITS MODULATION BY MyoD, RETINOIC ACID, AND TRANSFORMING GROWTH FACTOR-beta J. Biol. Chem., January 3, 2003; 278(1): 382 - 390. [Abstract] [Full Text] [PDF]

				J.-F. Ethier, P. G. Farnworth, J. K. Findlay, and G. T. Ooi Transforming Growth Factor-{beta} Modulates Inhibin A Bioactivity in the L{beta}T2 Gonadotrope Cell Line by Competing for Binding to Betaglycan Mol. Endocrinol., December 1, 2002; 16(12): 2754 - 2763. [Abstract] [Full Text] [PDF]

				C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]

				A. Bandyopadhyay, F. Lopez-Casillas, S. N. Malik, J. L. Montiel, V. Mendoza, J. Yang, and L-Z. Sun Antitumor Activity of a Recombinant Soluble Betaglycan in Human Breast Cancer Xenograft Cancer Res., August 15, 2002; 62(16): 4690 - 4695. [Abstract] [Full Text] [PDF]

				D. J. Bernard, S. C. Chapman, and T. K. Woodruff Minireview: Inhibin Binding Protein (InhBP/p120), Betaglycan, and the Continuing Search for the Inhibin Receptor Mol. Endocrinol., February 1, 2002; 16(2): 207 - 212. [Abstract] [Full Text] [PDF]