J. Cell Biol., Volume 141, Number 1, April 6, 1998 241-253

Activation of Distinct ₅₁-mediated Signaling Pathways by Fibronectin's Cell Adhesion and Matrix Assembly Domains

Denise C. Hocking, Jane Sottile, and Paula J. McKeown-Longo

Department of Physiology and Cell Biology, Albany Medical College, Albany, New York 12208

The interaction of cells with fibronectin generates a series of complex signaling events that serve to regulate several aspects of cell behavior, including growth, differentiation, adhesion, and motility. The formation of a fibronectin matrix is a dynamic, cell-mediated process that involves both ligation of the ₅₁ integrin with the Arg-Gly-Asp (RGD) sequence in fibronectin and binding of the amino terminus of fibronectin to cell surface receptors, termed "matrix assembly sites," which mediate the assembly of soluble fibronectin into insoluble fibrils. Our data demonstrate that the amino-terminal type I repeats of fibronectin bind to the ₅₁ integrin and support cell adhesion. Furthermore, the amino terminus of fibronectin modulates actin assembly, focal contact formation, tyrosine kinase activity, and cell migration. Amino-terminal fibronectin fragments and RGD peptides were able to cross-compete for binding to the ₅₁ integrin, suggesting that these two domains of fibronectin cannot bind to the ₅₁ integrin simultaneously. Cell adhesion to the amino-terminal domain of fibronectin was enhanced by cytochalasin D, suggesting that the ligand specificity of the ₅₁ integrin is regulated by the cytoskeleton. These data suggest a new paradigm for integrin-mediated signaling, where distinct regions within one ligand can modulate outside-in signaling through the same integrin.

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

This article has been cited by other articles:

• Mohseni, M., Chishti, A. H. (2008). The Headpiece Domain of Dematin Regulates Cell Shape, Motility, and Wound Healing by Modulating RhoA Activation. Mol. Cell. Biol. 28: 4712-4718 [Abstract] [Full Text]  
• Desban, N., Lissitzky, J.-C., Rousselle, P., Duband, J.-L. (2006). {alpha}1{beta}1-integrin engagement to distinct laminin-1 domains orchestrates spreading, migration and survival of neural crest cells through independent signaling pathways. J. Cell Sci. 119: 3206-3218 [Abstract] [Full Text]  
• Hocevar, B. A., Prunier, C., Howe, P. H. (2005). Disabled-2 (Dab2) Mediates Transforming Growth Factor {beta} (TGF{beta})-stimulated Fibronectin Synthesis through TGF{beta}-activated Kinase 1 and Activation of the JNK Pathway. J. Biol. Chem. 280: 25920-25927 [Abstract] [Full Text]  
• Wei, Y., Czekay, R.-P., Robillard, L., Kugler, M. C., Zhang, F., Kim, K. K., Xiong, J.-p., Humphries, M. J., Chapman, H. A. (2005). Regulation of {alpha}5{beta}1 integrin conformation and function by urokinase receptor binding. JCB 168: 501-511 [Abstract] [Full Text]  
• Monaghan, E., Gueorguiev, V., Wilkins-Port, C., McKeown-Longo, P. J. (2004). The Receptor for Urokinase-type Plasminogen Activator Regulates Fibronectin Matrix Assembly in Human Skin Fibroblasts. J. Biol. Chem. 279: 1400-1407 [Abstract] [Full Text]  
• Orecchia, A., Lacal, P. M., Schietroma, C., Morea, V., Zambruno, G., Failla, C. M. (2003). Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the {alpha}5{beta}1 integrin. J. Cell Sci. 116: 3479-3489 [Abstract] [Full Text]  
• Wilson, S. H., Ljubimov, A. V., Morla, A. O., Caballero, S., Shaw, L. C., Spoerri, P. E., Tarnuzzer, R. W., Grant, M. B. (2003). Fibronectin Fragments Promote Human Retinal Endothelial Cell Adhesion and Proliferation and ERK Activation through {alpha}5{beta}1 Integrin and PI 3-Kinase. IOVS 44: 1704-1715 [Abstract] [Full Text]  
• Sachchidanand, , Lequin, O., Staunton, D., Mulloy, B., Forster, M. J., Yoshida, K., Campbell, I. D. (2002). Mapping the Heparin-binding Site on the 13-14F3 Fragment of Fibronectin. J. Biol. Chem. 277: 50629-50635 [Abstract] [Full Text]  
• Wickstrom, S. A., Alitalo, K., Keski-Oja, J. (2002). Endostatin Associates with Integrin {alpha}5{beta}1 and Caveolin-1, and Activates Src via a Tyrosyl Phosphatase-dependent Pathway in Human Endothelial Cells. Cancer Res. 62: 5580-5589 [Abstract] [Full Text]  
• Sottile, J., Hocking, D. C. (2002). Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions. Mol. Biol. Cell 13: 3546-3559 [Abstract] [Full Text]  
• Salicioni, A. M., Mizelle, K. S., Loukinova, E., Mikhailenko, I., Strickland, D. K., Gonias, S. L. (2002). The Low Density Lipoprotein Receptor-related Protein Mediates Fibronectin Catabolism and Inhibits Fibronectin Accumulation on Cell Surfaces. J. Biol. Chem. 277: 16160-16166 [Abstract] [Full Text]  
• Esteban-Barragan, M. A., Avila, P., Alvarez-Tejado, M., Gutierrez, M. D., Garcia-Pardo, A., Sanchez-Madrid, F., Landazuri, M. O. (2002). Role of the von Hippel-Lindau Tumor Suppressor Gene in the Formation of {beta}1-Integrin Fibrillar Adhesions. Cancer Res. 62: 2929-2936 [Abstract] [Full Text]  
• Akimov, S. S., Belkin, A. M. (2002). Cell-surface transglutaminase promotes fibronectin assembly via interaction with the gelatin-binding domain of fibronectin: a role in TGF{beta}-dependent matrix deposition. J. Cell Sci. 114: 2989-3000 [Abstract] [Full Text]  
• Lishko, V. K., Yakubenko, V. P., Hertzberg, K. M., Grieninger, G., Ugarova, T. P. (2001). The alternatively spliced {alpha}EC domain of human fibrinogen-420 is a novel ligand for leukocyte integrins {alpha}M{beta}2 and {alpha}X{beta}2. Blood 98: 2448-2455 [Abstract] [Full Text]  
• Naruishi, K., Takashiba, S., Nishimura, F., Chou, H.-H., Arai, H., Yamada, H., Murayama, Y. (2001). Impairment of Gingival Fibroblast Adherence by IL-6/sIL-6R. JDR 80: 1421-1424 [Abstract]  
• Craig, D., Krammer, A., Schulten, K., Vogel, V. (2001). Comparison of the early stages of forced unfolding for fibronectin type III modules. Proc. Natl. Acad. Sci. USA 10.1073/pnas.101582198v1 [Abstract] [Full Text]  
• Davenpeck, K. L., Marcinkiewicz, C., Wang, D., Niculescu, R., Shi, Y., Martin, J. L., Zalewski, A. (2001). Regional Differences in Integrin Expression : Role of {{alpha}}5{beta}1 in Regulating Smooth Muscle Cell Functions. Circ. Res. 88: 352-358 [Abstract] [Full Text]  
• Akimov, S. S., Krylov, D., Fleischman, L. F., Belkin, A. M. (2000). Tissue Transglutaminase Is an Integrin-binding Adhesion Coreceptor for Fibronectin. JCB 148: 825-838 [Abstract] [Full Text]  
• Sottile, J, Hocking, D., Langenbach, K. (2000). Fibronectin polymerization stimulates cell growth by RGD-dependent and -independent mechanisms. J. Cell Sci. 113: 4287-4299 [Abstract]  
• Schedin, P, Strange, R, Mitrenga, T, Wolfe, P, Kaeck, M (2000). Fibronectin fragments induce MMP activity in mouse mammary epithelial cells: evidence for a role in mammary tissue remodeling. J. Cell Sci. 113: 795-806 [Abstract]  
• Disatnik, M.-H., Rando, T. A. (1999). Integrin-mediated Muscle Cell Spreading. THE ROLE OF PROTEIN KINASE C IN OUTSIDE-IN AND INSIDE-OUT SIGNALING AND EVIDENCE OF INTEGRIN CROSS-TALK. J. Biol. Chem. 274: 32486-32492 [Abstract] [Full Text]  
• Hocking, D. C., Sottile, J., Reho, T., Fassler, R., McKeown-Longo, P. J. (1999). Inhibition of Fibronectin Matrix Assembly by the Heparin-binding Domain of Vitronectin. J. Biol. Chem. 274: 27257-27264 [Abstract] [Full Text]  
• Hu, D. D., White, C. A., Panzer-Knodle, S., Page, J. D., Nicholson, N., Smith, J. W. (1999). A New Model of Dual Interacting Ligand Binding Sites on Integrin alpha IIbbeta 3. J. Biol. Chem. 274: 4633-4639 [Abstract] [Full Text]  
• Schor, S., Ellis, I, Banyard, J, Schor, A. (1999). Motogenic activity of IGD-containing synthetic peptides. J. Cell Sci. 112: 3879-3888 [Abstract]  
• Christopher, R., Judge, S., Vincent, P., Higgins, P., McKeown-Longo, P. (1999). The amino-terminal matrix assembly domain of fibronectin stabilizes cell shape and prevents cell cycle progression. J. Cell Sci. 112: 3225-3235 [Abstract]  
• Moyano, J. V., Carnemolla, B., Albar, J. P., Leprini, A., Gaggero, B., Zardi, L., Garcia-Pardo, A. (1999). Cooperative Role for Activated alpha 4beta 1 Integrin and Chondroitin Sulfate Proteoglycans in Cell Adhesion to the Heparin III Domain of Fibronectin. IDENTIFICATION OF A NOVEL HEPARIN AND CELL BINDING SEQUENCE IN REPEAT III5. J. Biol. Chem. 274: 135-142 [Abstract] [Full Text]  
• Sottile, J, Hocking, D., Swiatek, P. (1998). Fibronectin matrix assembly enhances adhesion-dependent cell growth. J. Cell Sci. 111: 2933-2943 [Abstract]  
• Craig, D., Krammer, A., Schulten, K., Vogel, V. (2001). Comparison of the early stages of forced unfolding for fibronectin type III modules. Proc. Natl. Acad. Sci. USA 98: 5590-5595 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents