Potential Proteolytic Activity of Human Plasma Fibronectin: Fibronectin Gelatinase

Abstract

Human plasma fibronectin contains a latent proteinase that after activation cleaves gelatin and fibronectin. The autoactivation propensity of the two purified cathepsin D-produced fragments of fibronectin (190 and 120 kDa) was compared. Both polypeptides were spontaneously activated in the presence of Ca 2 ®. This activation was inhibited by EDTA. The active gelatinase was isolated from the autodigest of the 190-kDa fragment. Among various protein substrates, including laminin and native type I and IVcollagens, the purified enzyme degraded only gelatin and fibronectin. We have named this proteinase FN-gelatinase.

Migration‐stimulating factor displays HEXXH‐dependent catalytic activity important for promoting tumor cell migration

“…For instance, some Fn fragments exhibit catalytic activities. 5,7,[18][19][20][21][22] This is the case for the GBD, which displays zinc-dependent collagenase/gelatinase activity, 5,6 called Fn-proteinase. 4 We hypothesized that these cryptic activities of Fn domains may also arise from alternative splicing.…”

Deciphering cryptic proteases

“…Other fragments stimulate the expression of matrix metalloproteinases, tumor necrosis factor-a, tissue inhibitor of metalloproteinase 1 and urokinase type plasminogen activator [107][108][109]. Finally, several studies reported the existence of four different cryptic proteinases (as their physiological relevance is unknown as well as their proteolytic mechanism) in human pFN, designated as fibronectinase (a serine protease), FN-gelatinase and FN-lamininase (aspartic proteases) and FN-type IV collagenase (a metalloprotease) [110][111][112][113]. It is, however, noteworthy that the four enzymes in fibronectin, which we will next address in detail, need further characterization in order to unequivocally demonstrate their existence.…”

“…In addition to Fnase, human plasma fibronectin has been described as containing two additional latent aspartic proteinases, 111], similarly to retroviral aspartic proteinases.…”

“…FN-gelatinase and FN-lamininase[110,111], that similarly to Fnase have still uncharacterized structure and unclear physiological function. Both enzymes can be generated and activated in the presence of Ca 2+ from the 190-kDa FN fragment generated by digestion with cathepsin D[110,111].…”

“…Both enzymes can be generated and activated in the presence of Ca 2+ from the 190-kDa FN fragment generated by digestion with cathepsin D[110,111]. FN-gelatinase (35 kDa) is located in the central domain of FN and has denaturated collagen type IV[111] and fibronectin as preferential substrates. FN-lamininase (25 kDa) is located in the carboxy-terminal heparin-binding domain and preferentially cleaves laminin and denaturated collagen[110].…”