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

J. Biol. Chem., Vol. 280, Issue 30, 27970-27980, July 29, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/30/27970    most recent M504270200v1 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 Gregory, K. E. Articles by Sakai, L. Y. Search for Related Content PubMed PubMed Citation Articles by Gregory, K. E. Articles by Sakai, L. Y. Social Bookmarking                      What's this?

The Prodomain of BMP-7 Targets the BMP-7 Complex to the Extracellular Matrix^*

Kate E. Gregory, Robert N. Ono, Noe L. Charbonneau, Chiu-Liang Kuo¶, Douglas R. Keene, Hans Peter Bächinger¶, and Lynn Y. Sakai¶||

From the Shriners Hospital for Children and the ^¶Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239

Biochemical and biophysical methods are used to show that BMP-7 is secreted as a stable complex consisting of the processed growth factor dimer noncovalently associated with its two prodomain propeptide chains and that the BMP-7 complex is structurally similar to the small transforming growth factor (TGF) complex. Because the prodomain of TGF interacts with latent TGF-binding proteins, a family of molecules homologous to the fibrillins, the prodomain of BMP-7 was tested for binding to fibrillin-1 or to LTBP-1. The BMP-7 prodomain and BMP-7 complex, but not the separated growth factor dimer, interact with N-terminal regions of fibrillin-1. This interaction may target the BMP-7 complex to fibrillin microfibrils in the extracellular matrix. Immunolocalization of BMP-7 in tissues like the kidney capsule and skin reveals co-localization with fibrillin. However, BMP-7 immunolocalization in other tissues known to be active sites for BMP-7 signaling is not apparent, suggesting that immunolocalization of BMP-7 in certain tissues represents specific extracellular storage sites. These studies suggest that the prodomains of TGF-like growth factors are important for positioning and concentrating growth factors in the extracellular matrix. In addition, they raise the possibility that prodomains of other TGF-like growth factors interact with fibrillins and/or LTBPs and are also targeted to the extracellular matrix.

Received for publication, April 19, 2005 , and in revised form, May 24, 2005.

^* This work was supported by grants from the Shriners Hospitals for Children (to L. Y. S., H. P. B., and D. R. K.) and by National Institutes of Health Grants RO1AR46811 and PO1AR049698 (Project 2) (to L. Y. S.). 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.

Both authors contributed equally to this work.

^|| To whom correspondence should be addressed: Shriners Hospital for Children, 3101 SW Sam Jackson Park Rd., Portland, OR 97239. Tel.: 503-221-3436; Fax: 503-221-3451; E-mail: lys{at}shcc.org.

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

This article has been cited by other articles:

				J. S. Weinbaum, T. J. Broekelmann, R. A. Pierce, C. C. Werneck, F. Segade, C. S. Craft, R. H. Knutsen, and R. P. Mecham Deficiency in Microfibril-associated Glycoprotein-1 Leads to Complex Phenotypes in Multiple Organ Systems J. Biol. Chem., September 12, 2008; 283(37): 25533 - 25543. [Abstract] [Full Text] [PDF]

				G. Sengle, N. L. Charbonneau, R. N. Ono, T. Sasaki, J. Alvarez, D. R. Keene, H. P. Bachinger, and L. Y. Sakai Targeting of Bone Morphogenetic Protein Growth Factor Complexes to Fibrillin J. Biol. Chem., May 16, 2008; 283(20): 13874 - 13888. [Abstract] [Full Text] [PDF]

				F. Ploger, P. Seemann, M. Schmidt-von Kegler, K. Lehmann, J. Seidel, K. W. Kjaer, J. Pohl, and S. Mundlos Brachydactyly type A2 associated with a defect in proGDF5 processing Hum. Mol. Genet., May 1, 2008; 17(9): 1222 - 1233. [Abstract] [Full Text] [PDF]

				S. Saito, K. Yano, S. Sharma, H. E. McMahon, and S. Shimasaki Characterization of the post-translational modification of recombinant human BMP-15 mature protein Protein Sci., February 1, 2008; 17(2): 362 - 370. [Abstract] [Full Text] [PDF]

				H. E. McMahon, S. Sharma, and S. Shimasaki Phosphorylation of Bone Morphogenetic Protein-15 and Growth and Differentiation Factor-9 Plays a Critical Role in Determining Agonistic or Antagonistic Functions Endocrinology, February 1, 2008; 149(2): 812 - 817. [Abstract] [Full Text] [PDF]

				L. Wilkinson, T. Gilbert, G. Kinna, L.-A. Ruta, D. Pennisi, M. Kett, and M. H. Little Crim1KST264/KST264 Mice Implicate Crim1 in the Regulation of Vascular Endothelial Growth Factor-A Activity during Glomerular Vascular Development J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1697 - 1708. [Abstract] [Full Text] [PDF]

				C.-L. Kuo, Z. Isogai, D. R. Keene, N. Hazeki, R. N. Ono, G. Sengle, H. Peter Bachinger, and L. Y. Sakai Effects of Fibrillin-1 Degradation on Microfibril Ultrastructure J. Biol. Chem., February 9, 2007; 282(6): 4007 - 4020. [Abstract] [Full Text] [PDF]

				S. S. Chaudhry, S. A. Cain, A. Morgan, S. L. Dallas, C. A. Shuttleworth, and C. M. Kielty Fibrillin-1 regulates the bioavailability of TGF{beta}1 J. Cell Biol., January 29, 2007; 176(3): 355 - 367. [Abstract] [Full Text] [PDF]

				K. Bose, R. Nischt, A. Page, B. L. Bader, M. Paulsson, and N. Smyth Loss of Nidogen-1 and -2 Results in Syndactyly and Changes in Limb Development J. Biol. Chem., December 22, 2006; 281(51): 39620 - 39629. [Abstract] [Full Text] [PDF]

				S. Sopory, S. M. Nelsen, C. Degnin, C. Wong, and J. L. Christian Regulation of Bone Morphogenetic Protein-4 Activity by Sequence Elements within the Prodomain J. Biol. Chem., November 10, 2006; 281(45): 34021 - 34031. [Abstract] [Full Text] [PDF]

				P N Robinson, E Arteaga-Solis, C Baldock, G Collod-Beroud, P Booms, A De Paepe, H C Dietz, G Guo, P A Handford, D P Judge, et al. The molecular genetics of Marfan syndrome and related disorders J. Med. Genet., October 1, 2006; 43(10): 769 - 787. [Abstract] [Full Text] [PDF]

				B. D. Gelb Marfan's Syndrome and Related Disorders -- More Tightly Connected Than We Thought N. Engl. J. Med., August 24, 2006; 355(8): 841 - 844. [Full Text] [PDF]

				O. Yoshino, H. E. McMahon, S. Sharma, and S. Shimasaki A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse PNAS, July 11, 2006; 103(28): 10678 - 10683. [Abstract] [Full Text] [PDF]

				A. Shifren and R. P. Mecham The stumbling block in lung repair of emphysema: elastic fiber assembly. Proceedings of the ATS, July 1, 2006; 3(5): 428 - 433. [Abstract] [Full Text] [PDF]

				S. Mazerbourg and A. J.W. Hsueh Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands Hum. Reprod. Update, July 1, 2006; 12(4): 373 - 383. [Abstract] [Full Text] [PDF]

				M. Zeisberg Bone morphogenic protein-7 and the kidney: current concepts and open questions Nephrol. Dial. Transplant., March 1, 2006; 21(3): 568 - 573. [Full Text] [PDF]