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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May 01 1995
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,
D Gilat
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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R Hershkoviz,
R Hershkoviz
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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I Goldkorn,
I Goldkorn
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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L Cahalon,
L Cahalon
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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G Korner,
G Korner
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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I Vlodavsky,
I Vlodavsky
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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O Lider
O Lider
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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D Gilat
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
R Hershkoviz
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
I Goldkorn
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
L Cahalon
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
G Korner
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
I Vlodavsky
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
O Lider
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 181 (5): 1929–1934.
Citation
D Gilat, R Hershkoviz, I Goldkorn, L Cahalon, G Korner, I Vlodavsky, O Lider; 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.. J Exp Med 1 May 1995; 181 (5): 1929–1934. doi: https://doi.org/10.1084/jem.181.5.1929
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