Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.5 (
cathepsin D
)
4,130
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The alternatively spliced type III connecting segment (IIICS) of fibronectin (Fn) contains an amino acid sequence,
CS-1
, which is recognized by the integrin receptor, alpha 4 beta 1. Plasma Fn inhibits alpha 4 beta 1-dependent binding of lymphocytes and monocytes to
CS-1
containing Fn derivatives poorly, suggesting limited exposure of the
CS-1
sequence in Fn. To test the availability of
CS-1
in plasma Fn, an antibody was raised to the synthetic peptide
CS-1
. The
CS-1
sequence was found to be minimally exposed in plasma Fn; and immobilization of Fn, a model of matrix deposition, caused only a modest increase in its exposure. Digestion of Fn with selected proteases, however, induced substantial expression of the
CS-1
sequence. The acid protease
cathepsin D
generated fragments of 31-33.5 kDa from the COOH-terminal heparin-binding domain of Fn which possessed high immunoreactivity with anti-
CS-1
. Digestion of Fn with cathepsin B also resulted in the exposure of
CS-1
sequence in a 140 kDa fragment. Although the digestion of Fn with neutral proteases (neutrophil elastase, cathepsin G, chymotrypsin, trypsin) generated fragments from the COOH-terminal heparin-binding domain of similar molecular weight as with
cathepsin D
, the exposure of
CS-1
did not occur. Exposure of the
CS-1
region by the cathepsins was supported by cell adhesion experiments; digestion of Fn with cathepsins D and B transformed inert plasma Fn to an effective inhibitor of adhesion of lymphoblastoid B and T cells (Ramos, Jurkat, Molt-4) to an immobilized
CS-1
conjugate. These results suggest that exposure of the
CS-1
sequence in plasma Fn by proteolysis with cathepsins D and B, enzymes implicated in several pathological processes, may serve a regulatory function in cell adhesion. The adhesive function of the
CS-1
region in intact Fn appears to be suppressed by the native conformation of the molecule.
...
PMID:Proteolysis regulates exposure of the IIICS-1 adhesive sequence in plasma fibronectin. 871 84
