Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein.
Integrins are a complex family of divalent cation-dependent cell adhesion receptors composed of one alpha and one beta subunit noncovalently bound to one another. A subset of integrins contains the alpha v subunit in association with one of several beta subunits (e.g. beta 3, beta 5, beta 1). We have ... recently identified a novel integrin beta subunit, beta 6, that is present in a number of epithelial cell lines. Using a polyclonal antibody raised against the carboxyl-terminal peptide of beta 6, we have now identified the integrin heterodimer, alpha v beta 6, on the surface of two human carcinoma cell lines. Using affinity chromatography of lysates from the pancreatic carcinoma cell line, FG-2, we demonstrate that alpha v beta 6 binds to fibronectin, but not to vitronectin or collagen I. In contrast, the alpha v beta 5 integrin, which is also expressed on FG-2 cells, binds exclusively to vitronectin. Immobilized collagen I does not interact with alpha v integrins, but binds beta 1-containing integrins. Both alpha v beta 6 and alpha v beta 5 are eluted from their respective immobilized ligands by a hexa-peptide containing the sequence Arg-Gly-Asp (RGD). RGD is highly effective in the presence of Ca2+, somewhat less effective in Mg2+, and virtually inactive in Mn2+. These results suggest that alpha v beta 6 functions as an RGD-dependent fibronectin receptor in FG-2 carcinoma cells. In agreement with this notion, cell adhesion assays show that FG-2 cell attachment to fibronectin is only partially inhibited by anti-beta 1 integrin antibodies, implying that other fibronectin receptors may be involved. Taken together with recent reports on the vitronectin receptor function of alpha v beta 5, our results suggest that the previously described carcinoma cell integrin, alpha v beta x (Cheresh, D. A., Smith, J. W., Cooper, H. M., and Quaranta, V. (1989) Cell 57, 59-69), is a mixture of at least two different receptors: alpha v beta 5, mediating adhesion to vitronectin, and alpha v beta 6, mediating adhesion to fibronectin.
Mesh Terms:
Amino Acid Sequence, Antigens, Neoplasm, Cell Line, Cell Membrane, Chromatography, Affinity, Electrophoresis, Polyacrylamide Gel, Fibronectins, Humans, Integrins, Kinetics, Lung Neoplasms, Macromolecular Substances, Molecular Sequence Data, Pancreatic Neoplasms, Receptors, Fibronectin, Receptors, Immunologic, Substrate Specificity
Amino Acid Sequence, Antigens, Neoplasm, Cell Line, Cell Membrane, Chromatography, Affinity, Electrophoresis, Polyacrylamide Gel, Fibronectins, Humans, Integrins, Kinetics, Lung Neoplasms, Macromolecular Substances, Molecular Sequence Data, Pancreatic Neoplasms, Receptors, Fibronectin, Receptors, Immunologic, Substrate Specificity
J. Biol. Chem.
Date: Mar. 25, 1992
PubMed ID: 1532572
View in: Pubmed Google Scholar
Download Curated Data For This Publication
3269
Switch View:
- Interactions 2