|
|
||||||||
vß6-mediated activation of latent TGF-ß complexes containing LTBP-1



,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:
![]() |
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] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |