Cells possess recognition mechanisms that allow them to adhere to extracellular matrices and to one another. These adhesion mechanisms furnish important regulatory signals to the cells. In addition to anchoring cells, the adhesive interactions affect cellular responses such as migration and differentiation. Aberrations in adhesion play an important role in the invasive behavior of malignant cells. This project examines the molecular biology of an important component of cell adhesion, cell-extraceellular matrix interactions. Specifically, the interaction of cells with extracellular matrix proteins, such as fibronectin and laminin, through two closely related adhesion receptors or integrins in being stuided. These receptors appear to share one subunit (beta) and have one distinct subunit (alpha). This structural relationship will be verified by cloning the laminin receptor and receptors composed of portions of each receptor will be expressed in mammalian test cells and the ability of such cells to attach and migrate on viarious substrates will be tested. The interactions of the cytoplasmic domains of the receptors will be examined to derive information on possible intracellular signalling through the receptors. Finally, the extent of structural and functional heterogeneity among the integrin superfamily and the mechanisms whereby the receptor affinity for its ligand is regulated in cells will be studied by cloning additional receptors and by studying the specificity of the same receptor from various types of cells. These studies, which are conducted in collaboration with other participants of the program project, will help clarify the role of cell adhesion in normal and malignant cells.
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