Fibronectin is required for integrin αvß6-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@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 αvß6. 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 α5ß1 exhibit defective activation of latent TGF-ß by αvß6 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 αvß6-mediated activation of latent TGF-ß complexes containing LTBP-1. Key Words: LTBP • TGF-ß • fibronectin null cells
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Fibronectin is required for integrin αvß6-mediated activation of latent TGF-ß complexes containing LTBP-1
Fontana, Laura; Chen, Yan; Prijatelj, Petra; Sakai, Takao; Fässler, Reinhard; Sakai, Lynn Y.; Rifkin, Daniel B.
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, Volume 19 (13): 1798
Fed of American Socs for Experimental Biology – Nov 1, 2005
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