Molecular behavior adapts to context: heparanase functions as an extracellular matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local pH …

D Gilat, R Hershkoviz, I Goldkorn, L Cahalon… - The Journal of …, 1995 - rupress.org
D Gilat, R Hershkoviz, I Goldkorn, L Cahalon, G Korner, I Vlodavsky, O Lider
The Journal of experimental medicine, 1995rupress.org
Migration of lymphocytes into inflammatory sites requires their adhesion to the vascular
endothelium and subendothelial extracellular matrix (ECM). The ensuing penetration of the
ECM is associated with the expression of ECM-degrading enzymes, such as endo-beta-D
glucuronidase (heparanase), which cleaves heparan sulfate (HS) proteoglycans. We now
report that, depending on the local pH, a mammalian heparanase can function either as an
enzyme or as an adhesion molecule. At relatively acidified pH conditions, heparanase …
Migration of lymphocytes into inflammatory sites requires their adhesion to the vascular endothelium and subendothelial extracellular matrix (ECM). The ensuing penetration of the ECM is associated with the expression of ECM-degrading enzymes, such as endo-beta-D glucuronidase (heparanase), which cleaves heparan sulfate (HS) proteoglycans. We now report that, depending on the local pH, a mammalian heparanase can function either as an enzyme or as an adhesion molecule. At relatively acidified pH conditions, heparanase performs as an enzyme, degrading HS. In contrast, at the hydrogen ion concentration of a quiescent tissue, heparanase binds specifically to HS molecules without degrading them, and thereby anchors CD4+ human T lymphocytes. Thus, the local state of a tissue can regulate the activities of heparanase and can determine whether the molecule will function as an enzyme or as a proadhesive molecule.
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