Epiligrin, an epithelial ligand for integrins

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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435325, 4353201, 536 235, C12Q 168

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061209910

DESCRIPTION:

BRIEF SUMMARY
1. FIELD OF THE INVENTION

The invention relates generally to epithelial cell receptors and ligands which are useful for adhering epithelial cells to a substratum.


2. BACKGROUND OF THE INVENTION

The invention is predicated upon a basic understanding of epithelial cells and tissues studied. Such epithelia, which cover free surfaces and line body cavities and ducts, have been studied microscopically for at least three centuries. Recently the biochemistry and molecular biology of epithelial cells and tissues have been extensively investigated. However, the seemingly simple question of how the cells in epithelial tissues are driven to become specialized has remained unanswered. The present invention provides reagents that allow us for the first time to unravel the inter- and intracellular signals that direct epithelial cell differentiation. More fundamentally, the subject reagents permit one to finally decipher what has been a tangled web of suspected interactions involving a wide variety of cell types, some of them non-epithelial, in order to understand and modulate at a molecular level how the cells are driven to differentiate to fulfill specialized functions in the body. Pertinent background information concerning these heretofore disparate systems follows.
2.1 Abbreviations
By way of introduction, the following abbreviations are used in this disclosure: BPA, bullous pemphigoid antigen; CD3, cellular determinant #3, a lymphocyte surface antigen marker; CP, cicatrical pemphigoid, an autoimmune dermatological disease; EBA, epidermolysis bullosa acquisita, an autoimmune dermatological disease; ECM, extracellular matrix; FAs, focal adhesions; HD-BSA, heat denatured bovine serum albumin; HFK(s), human foreskin keratinocyte(s); HFK-ECM, human foreskin keratinocyte-extracellular matrix; kDa, kilodaltons of molecular mass as determined by SDS-PAGE; MAbs, monoclonal antibodies; Mr, molecular radius by SDS-PAGE, approximating molecular mass; SACs, stable anchoring contacts; and SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
E200, E170, E145, E135, E100, and E36 refer to the constituent and associated glycoproteins of the subject epithelial ligand complex epiligrin, having apparent molecular weights of 200.+-.20 kDa, 170.+-.20 kDa, 145.+-.20 kDa, 135.+-.15 kDa, 100.+-.10 kDa, and 36.+-.5 kDa, respectively.
Ep-1, 1-1, and 8-6 refer to the disclosed cDNA clones deposited under ATCC accession numbers 75540, 75539, and 75538, respectively.
Throughout the specification, the notation "(#)" is used to refer to the documents listed in the appended Citations section.
2.2 Epithelial Cells
The invention is predicated upon a basic understanding of epithelial cells and tissues studied. Such epithelia, which cover free surfaces and line body cavities and ducts, have been studied microscopically for at least three centuries. Recently the biochemistry and molecular biology of epithelial cells and tissues have been extensively investigated. However, the seemingly simple question of how the cells in epithelial tissues are driven to become specialized has remained unanswered. The present invention provides reagents that allow us for the first time to unravel the inter- and intracellular signals that direct epithelial cell differentiation. More fundamentally, the subject reagents permit one to finally decipher what has been a tangled web of suspected interactions involving a wide variety of cell types, some of them nonepithelial, in order to understand and modulate at a molecular level how these cells are driven to differentiate to fulfill their specialized functions in the body. Pertinent background information concerning these heretofore disparate systems follows.
The significance of epithelial tissues as a protective barrier is readily apparent in the body as the lining of body cavities, blood vessels, digestive tract, mammary glands, urogenital, endocrine, reticuloendothelial systems, respiratory surfaces, placenta, and surrounding the nerves and brain. The epithelia also forms the basis for the epidermis, co

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