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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Fontana, L. Articles by Rifkin, D. B. Search for Related Content PubMed PubMed Citation Articles by Fontana, L. Articles by Rifkin, D. B.

Fibronectin is required for integrin vß6-mediated activation of latent TGF-ß complexes containing LTBP-1

Laura Fontana^*, Yan Chen^*, Petra Prijatelj^*, Takao Sakai, Reinhard Fässler, Lynn Y. Sakai and Daniel B. Rifkin^*,,1

Departments of
^* Cell Biology and
Medicine, New York University School of Medicine, New York, New York, USA; Shriners Hospital for Children and
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon, USA; and Max Planck Institute of Biochemistry,
Department of Molecular Medicine, Martinsried, Germany

¹ Correspondence: Department of Cell Biology, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA. E-mail: rifkid01{at}med.nyu.edu

Transforming growth factor-ßs (TGF-ß) are secreted as latent complexes consisting of the TGF-ß dimer, the TGF-ß propeptide dimer, and the latent TGF-ß binding protein (LTBP). Although the bonds between TGF-ß and its propeptide are cleaved intracellulary, the propeptide associates with TGF-ß by electrostatic interactions, thereby conferring latency to the complex. We reported that a specific sequence of LTBP-1 is required for latent TGF-ß activation by the integrin vß6. Here we describe a 24 amino acid sequence from the hinge domain required for activation. The LTBP-1 polypeptide rL1N, which includes the hinge, associates with fibronectin in binding assays. We present evidence that fibronectin null cells minimally activate latent TGF-ß and poorly incorporate the active hinge sequence into their matrix. In addition, cells missing the fibronectin receptor 5ß1 exhibit defective activation of latent TGF-ß by vß6 and decreased matrix incorporation. The results indicate specificity for integrin-mediated latent TGF-ß activation that include unique sequences in LTBP-1 and an appropriate matrix molecule.—Fontana, L., Chen, Y., Prijatelj, P., Sakai, T., Fässler, R., Sakai, L. Y., Rifkin, D. B. Fibronectin is required for integrin vß6-mediated activation of latent TGF-ß complexes containing LTBP-1.

Key Words: LTBP • TGF-ß • fibronectin null cells

This article has been cited by other articles:

				R. N. Ono, G. Sengle, N. L. Charbonneau, V. Carlberg, H. P. Bachinger, T. Sasaki, S. Lee-Arteaga, L. Zilberberg, D. B. Rifkin, F. Ramirez, et al. Latent Transforming Growth Factor {beta}-binding Proteins and Fibulins Compete for Fibrillin-1 and Exhibit Exquisite Specificities in Binding Sites J. Biol. Chem., June 19, 2009; 284(25): 16872 - 16881. [Abstract] [Full Text] [PDF]

				Y. Kim, M. C. Kugler, Y. Wei, K. K. Kim, X. Li, A. N. Brumwell, and H. A. Chapman Integrin {alpha}3{beta}1-dependent {beta}-catenin phosphorylation links epithelial Smad signaling to cell contacts J. Cell Biol., January 26, 2009; 184(2): 309 - 322. [Abstract] [Full Text] [PDF]

				Y. Zhou, K. Koli, J. S. Hagood, M. Miao, M. Mavalli, D. B. Rifkin, and J. E. Murphy-Ullrich Latent Transforming Growth Factor-{beta}-Binding Protein-4 Regulates Transforming Growth Factor-{beta}1 Bioavailability for Activation by Fibrogenic Lung Fibroblasts in Response to Bleomycin Am. J. Pathol., January 1, 2009; 174(1): 21 - 33. [Abstract] [Full Text] [PDF]

				K. Yoshinaga, H. Obata, V. Jurukovski, R. Mazzieri, Y. Chen, L. Zilberberg, D. Huso, J. Melamed, P. Prijatelj, V. Todorovic, et al. Perturbation of transforming growth factor (TGF)-ss1 association with latent TGF-{beta} binding protein yields inflammation and tumors PNAS, December 2, 2008; 105(48): 18758 - 18763. [Abstract] [Full Text] [PDF]

				A. C. Liu and A. I. Gotlieb Transforming Growth Factor-{beta} Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells Am. J. Pathol., November 1, 2008; 173(5): 1275 - 1285. [Abstract] [Full Text] [PDF]

				Q. Chen, P. Sivakumar, C. Barley, D. M. Peters, R. R. Gomes, M. C. Farach-Carson, and S. L. Dallas Potential Role for Heparan Sulfate Proteoglycans in Regulation of Transforming Growth Factor-beta (TGF-beta) by Modulating Assembly of Latent TGF-beta-binding Protein-1 J. Biol. Chem., September 7, 2007; 282(36): 26418 - 26430. [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]