Abstract

This program examines the communication of cells with extracellular matrices. It is a close collaboration among investigators whose specialties range from cell and molecular biology to crystallography and NMR. In the project this wide range of expertise is brought to bear on the molecular mechanisms of cell-matrix recognition. The work centers around the RGD cell adhesion sequence originally discovered under this grant and its recognition by integrins. Peptide display libraries will be used as a source of peptides that will mimic the integrin-binding site in integrin-ligand interaction, the binding of the alpha5beta1 integrin to fibronectin, in particular. Physical methods will be applied to the study of the integrin-binding portions of fibronectin and the fibronectin- binding portions of the receptor for fibronectin. The integrin-binding will be related interactions between various parts of fibronectin that may compete with the integrin-binding. These studies will provide new information on integrin-ligand interactions and may help in the design of improved probes for the roles of integrins in malignancies and other diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA028896-14A1
Application #
2087834
Study Section
Special Emphasis Panel (SRC (CC))
Project Start
1981-07-01
Project End
1998-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
14
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

McLean, G W; Brown, K; Arbuckle, M I et al. (2001) Decreased focal adhesion kinase suppresses papilloma formation during experimental mouse skin carcinogenesis. Cancer Res 61:8385-9
Assa-Munt, N; Jia, X; Laakkonen, P et al. (2001) Solution structures and integrin binding activities of an RGD peptide with two isomers. Biochemistry 40:2373-8
Baneres, J L; Roquet, F; Martin, A et al. (2000) A minimized human integrin alpha(5)beta(1) that retains ligand recognition. J Biol Chem 275:5888-903
Ellerby, H M; Arap, W; Ellerby, L M et al. (1999) Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5:1032-8
Wang, B; Yang, H; Liu, Y C et al. (1999) Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display. Biochemistry 38:12499-504
Miura, R; Aspberg, A; Ethell, I M et al. (1999) The proteoglycan lectin domain binds sulfated cell surface glycolipids and promotes cell adhesion. J Biol Chem 274:11431-8
Ruoslahti, E (1999) Fibronectin and its integrin receptors in cancer. Adv Cancer Res 76:1-20
Orend, G; Hunter, T; Ruoslahti, E (1998) Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells. Oncogene 16:2575-83
Kodandapani, R; Veerapandian, L; Ni, C Z et al. (1998) Conformational change in an anti-integrin antibody: structure of OPG2 Fab bound to a beta 3 peptide. Biochem Biophys Res Commun 251:61-6
Arap, W; Pasqualini, R; Ruoslahti, E (1998) Chemotherapy targeted to tumor vasculature. Curr Opin Oncol 10:560-5

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