Major progress has been made in determining the chemical nature of the cell attachment site of fibronectin by using synthetic peptides and cloned cDNA. Our studies to determine if vitronectin may substitute for fibronectin in transformed cells that lack cell surface fibronectin and other matrix components by studying its function at the surfaces of transformed cells has also progressed well. We have succeeded in isolating a cell surface receptor for fibronectin. This is a 140 kd glycoprotein which, when incorporated into liposomes, confers them with an ability to attach to a fibronectin-coated surface. The vitronectin studies have progressed to a point where we have been able to clone the cDNA for this adhesion protein. This cDNA has allowed us to determine the complete amino acid sequence of vitronectin. The sequence shows that the cell attachment site of vitronectin is the same Arg-Gly-Asp sequence as that of fibronectin. We have also found that despite the similarity of the cell attachment sites of fibronectin and vitronectin, these proteins are recognized by different cell surface receptors which nevertheless have related specificities because they both recognize peptides containing the Arg-Gly-Asp sequence. We are now isolating cDNA clones for the fibronectin and vitronectin receptors to determine the structure of the receptor proteins. By using polypeptides coded for by the cloned cDNAs, we will determine which part of the polypeptide contains the site that interacts with the Arg-Gly-Asp sequence. This will allow comparison of the binding site structures in the two receptors. Our long-term goal is to regulate the synthesis of the receptors in tumor cells to determine whether their increased or decreased expression will affect the biological properties of the cells. (V)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA028896-07
Application #
3093269
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1981-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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