Localization of the ceavage sites on fibronectin following digestion by urokinase

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Abstract
Urokinase (u‐PA) proteolytically cleaves both human plasma (pFn) and cellular (cFn) dimeric fibronectin (Mr 440,000) into four major polypeptides of approximately Mr 210,000, 200,000, 25,000, and 6,000. Amino acid sequence analysis of the polypeptide fragments indicated that the enzymatic cleavage of Fn occurs at two sites: (1) between an arginine/alanine peptide bond located C‐terminal to residue 259; this cleavage liberates the N‐terminal Mr 25,000 fragment and the Mr 210,000 and Mr 200,000 polypeptides derived from the A and B chains of Fn, respectively; and (2) between an arginine/threonine peptide bond located C‐terminal to residue 2,299, thereby yielding an Mr 6,000 dimeric fragment containing the C‐terminal interchain disulfide bonds. Predigestion of Fn with u‐PA increased the molecule's vulnerability to further attack by the enzymes plasmin and cathepsin D. These data provide further biochemical evidence for the proteolytic cleavage of fibronectin by plasminogen activators and substantiate that u‐PA digestion of Fn may be an intial event in the local degradation of the extracellular matrix by malignant cells, possessing elevated levels of these enzymes.

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