Localization of the ceavage sites on fibronectin following digestion by urokinase
Author(s) -
Gold Leslie I.,
Rostagno Agueda,
Frangione Blas,
Passalaris Tina
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240500412
Subject(s) - fibronectin , digestion (alchemy) , urokinase , chemistry , microbiology and biotechnology , biochemistry , biology , medicine , chromatography , extracellular matrix
Abstract Urokinase (u‐PA) proteolytically cleaves both human plasma (pFn) and cellular (cFn) dimeric fibronectin (M r 440,000) into four major polypeptides of approximately M r 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 M r 25,000 fragment and the M r 210,000 and M r 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 M r 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. © 1992 Wiley‐Liss, Inc.