1. We will investigate the expression of different forms of fibronectin (FN) in different cell types and physiological situations. Particular attention will be paid to oncogenic transformation. These studies will use nucleic acid probes and antibodies which distinguish different spliced forms of FN. 2. We will investigate the control of alternative splicing by studies using the transcripts of selected segments of the FN gene and in vitro nuclear extracts. 3. We will use fragments, fusion proteins, specific antibodies and synthetic peptides to analyze the functions of specific segments of FN, particularly those which are alternatively spliced. 4. We will use retroviral expression vectors to analyze structure- function relationships of different forms of FN and of different segments of FN. 5. We will begin to apply the same approaches to studies of the integrin family of cell surface receptors which include receptors for FN and other matrix proteins. These studies should reveal the control mechanisms which determine the pattern of alternative splicing of FN and provide insights into the functional consequences of the differences between FN molecules which are produced by this process. These studies should also provide information on functions of regions of FN whose role is currently unknown. Finally, we should be able to gain further insights into the functions of cell surface receptors for FN.
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