Fibronectin Type III Repeats Mediate RGD-independent Adhesion and Signaling through Activated β1 Integrins*
- Gloria Chi-Rosso‡,
- Philip J. Gotwals‡,
- Jianliang Yang,
- Leona Ling,
- Kate Jiang,
- Betty Chao,
- Darren P. Baker,
- Linda C. Burkly,
- Stephen E. Fawell and
- Victor E. Koteliansky§
Abstract
Many cell-surface and extracellular matrix proteins contain multiple modular domains known as fibronectin type III (FNIII) repeats. Cells adhere to the extracellular matrix proteins fibronectin and tenascin in part by the interaction of certain integrins with the Arg-Gly-Asp (RGD) sequence, displayed on specific FNIII repeats. We have found that, after experimental activation of β1 integrins, a number of cell types adhere and spread on FNIII repeats lacking RGD, derived from extracellular matrix proteins and cytokine receptors. Interaction between individual FNIII domains and β1 integrins mediates focal adhesion kinase phosphorylation and subsequent stress fiber and focal contact formation. These data suggest that many FNIII-containing proteins may bind and signal through activated β1 integrins, dramatically expanding the potential for integrin-dependent intercellular and cell-matrix communication.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Contributed equally to this work.
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↵§ To whom correspondence should be addressed: Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142. Tel.: 617-679-3362; Fax: 617-679-2616.
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↵1 The abbreviations used are: ECM, extracellular matrix; FNIII, fibronectin type III; PMA, phorbol 12-myristate 13-acetate; mAb, monoclonal antibody; IL, interleukin; FAK, focal adhesion kinase.
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↵2 G. Chi-Rosso, P. J. Gotwals, V. E. Koteliansky, and J. Yang, unpublished data.
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- Received August 5, 1997.
- Revision received September 29, 1997.
