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

J. Biol. Chem., Vol. 283, Issue 12, 7628-7637, March 21, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/12/7628    most recent M704883200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kirkbride, K. C. Articles by Blobe, G. C. Search for Related Content PubMed PubMed Citation Articles by Kirkbride, K. C. Articles by Blobe, G. C. Social Bookmarking                      What's this?

Bone Morphogenetic Proteins Signal through the Transforming Growth Factor-β Type III Receptor^*

Kellye C. Kirkbride, Todd A. Townsend, Monique W. Bruinsma^¶, Joey V. Barnett, and Gerard C. Blobe^¶1

From the Departments of Pharmacology and Cancer Biology and ^¶Medicine, Duke University, Durham, North Carolina 27708 and the Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232

The bone morphogenetic protein (BMP) family, the largest subfamily of the structurally conserved transforming growth factor-β (TGF-β) superfamily of growth factors, are multifunctional regulators of development, proliferation, and differentiation. The TGF-β type III receptor (TβRIII or betaglycan) is an abundant cell surface proteoglycan that has been well characterized as a TGF-β and inhibin receptor. Here we demonstrate that TβRIII functions as a BMP cell surface receptor. TβRIII directly and specifically binds to multiple members of the BMP subfamily, including BMP-2, BMP-4, BMP-7, and GDF-5, with similar kinetics and ligand binding domains as previously identified for TGF-β. TβRIII also enhances ligand binding to the BMP type I receptors, whereas short hairpin RNA-mediated silencing of endogenous TβRIII attenuates BMP-mediated Smad1 phosphorylation. Using a biologically relevant model for TβRIII function, we demonstrate that BMP-2 specifically stimulates TβRIII-mediated epithelial to mesenchymal cell transformation. The ability of TβRIII to serve as a cell surface receptor and mediate BMP, inhibin, and TGF-β signaling suggests a broader role for TβRIII in orchestrating TGF-β superfamily signaling.

Received for publication, June 13, 2007 , and in revised form, January 9, 2008.

^* This work was supported by a predoctoral fellowship from the Department of Defense Breast Cancer Research Program (to K. C. K.), Vanderbilt University Grant GM007628 (to T. A. T.), and National Institutes of Health Grants HL52922 (to J. V. B.) and CA106307 (to G. C. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1-S4 and Figs. S1-S3.

¹ To whom correspondence should be addressed: 354 LSRC Research Dr., Box 91004 DUMC, Durham, NC 27708. Tel.: 919-668-1352; Fax: 919-681-6906; E-mail: blobe001{at}mc.duke.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Wiater, K. A. Lewis, C. Donaldson, J. Vaughan, L. Bilezikjian, and W. Vale Endogenous Betaglycan Is Essential for High-Potency Inhibin Antagonism in Gonadotropes Mol. Endocrinol., July 1, 2009; 23(7): 1033 - 1042. [Abstract] [Full Text] [PDF]

				N. E. Freeman-Anderson, Y. Zheng, A. C. McCalla-Martin, L. M. Treanor, Y. D. Zhao, P. M. Garfin, T.-C. He, M. N. Mary, J. D. Thornton, C. Anderson, et al. Expression of the Arf tumor suppressor gene is controlled by Tgf{beta}2 during development Development, June 15, 2009; 136(12): 2081 - 2089. [Abstract] [Full Text] [PDF]

				K. Mythreye and G. C. Blobe The type III TGF-{beta} receptor regulates epithelial and cancer cell migration through {beta}-arrestin2-mediated activation of Cdc42 PNAS, May 19, 2009; 106(20): 8221 - 8226. [Abstract] [Full Text] [PDF]

				M. Bilandzic, S. Chu, P. G. Farnworth, C. Harrison, P. Nicholls, Y. Wang, R. M. Escalona, P. J. Fuller, J. K. Findlay, and K. L. Stenvers Loss of Betaglycan Contributes to the Malignant Properties of Human Granulosa Tumor Cells Mol. Endocrinol., April 1, 2009; 23(4): 539 - 548. [Abstract] [Full Text] [PDF]

				K. J. Gordon, K. C. Kirkbride, T. How, and G. C. Blobe Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2 Carcinogenesis, February 1, 2009; 30(2): 238 - 248. [Abstract] [Full Text] [PDF]

				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]