Laminin and entactin and major components of basement membranes. It is well documented that laminin mediated cell adhesion and spreading, neurite outgrowth and neuronal survival. There is also evidence to suggest that it is involved in axonal guidance, formation of neuromuscular junctions, kidney development, embryogenesis and maintenance of differentiated functions. The interactions of laminin and its receptor has been implicated in the metastatic process and in the recognition of natural killer lymphocytes and their target cells. The involvement of entactin in the function of basement membranes is less clear. It found in tight non-covalent association with laminin and recent evidence suggests that it may also be involved in cell attachment. The objectives of this proposal are to (a) define the structures in laminin that are required for cell attachment. (b) isolate and characterize the cell surface molecules the mediate laminin binding, (c) clarify the role of entactin in basement membrane function especially with respect to cell attachment and (d) explore the regulation of expression of the laminin binding macromolecules. The primary sequences of laminin and entactin will be determined by recombinant DNA techniques. Fusion proteins containing segments of each molecule will be generated to be used as probes for cell binding and as antigens. Polyclonal and monoclonal antibodies produced with the fusion proteins and polypeptides derived from laminin and entactin will be employed to eluctidate their bindings domains. The long range objective of the project is to define the mechanisms whereby the extracellular matrix influences the behavior of cells during metastasis, embryogenesis and cellular differentiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA021246-12
Application #
3165501
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1978-02-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Dong, Lijin; Chen, Yong; Lewis, Marcia et al. (2002) Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1. Lab Invest 82:1617-30
Gresham, H D; Graham, I L; Griffin, G L et al. (1996) Domain-specific interactions between entactin and neutrophil integrins. G2 domain ligation of integrin alpha3beta1 and E domain ligation of the leukocyte response integrin signal for different responses. J Biol Chem 271:30587-94
Durkin, M E; Wewer, U M; Chung, A E (1995) Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene. Genomics 26:219-28
Dong, L J; Hsieh, J C; Chung, A E (1995) Two distinct cell attachment sites in entactin are revealed by amino acid substitutions and deletion of the RGD sequence in the cysteine-rich epidermal growth factor repeat 2. J Biol Chem 270:15838-43
Wu, C; Chung, A E; McDonald, J A (1995) A novel role for alpha 3 beta 1 integrins in extracellular matrix assembly. J Cell Sci 108 ( Pt 6):2511-23
Rasmussen, M V; Klein, N W; Abrahamson, D R et al. (1994) Effects of laminin monoclonal antibodies on the development of cultured rat embryos. Teratology 49:20-8
Donaldson, D J; Mahan, J T; Tsilibary, E C et al. (1994) Migratory interaction of amphibian epidermal cells with components of the basement membrane. J Cell Physiol 158:79-86
Hsieh, J C; Wu, C; Chung, A E (1994) The binding of fibronectin to entactin is mediated through the 29 kDa amino terminal fragment of fibronectin and the G2 domain of entactin. Biochem Biophys Res Commun 199:1509-17
Zagris, N; Stavridis, V; Chung, A E (1993) Appearance and distribution of entactin in the early chick embryo. Differentiation 54:67-71
Yelian, F D; Edgeworth, N A; Dong, L J et al. (1993) Recombinant entactin promotes mouse primary trophoblast cell adhesion and migration through the Arg-Gly-Asp (RGD) recognition sequence. J Cell Biol 121:923-9

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