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Cell surface binding of TIMP‐2 and pro‐MMP‐2/TIMP‐2 complex
Author(s) -
Emmert-Buck Michael R.,
Emonard HervéP.,
Corcoran Marta L.,
Krutzsch Henry C.,
Foidart Jean-Michel,
Stetler-Stevenson William G.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00345-a
Subject(s) - chemistry , matrix metalloproteinase , biophysics , microbiology and biotechnology , biochemistry , biology
Tissue inhibitor of metalloproteinases (TIMP‐2) is a low molecular weight proteinase inhibitor capable of inhibiting activated matrix metalloproteinases (MMPs). TIMP‐2 is found both free and in a 1:1 stoichiometric complex with the pro‐enzyme form of MMP‐2 (pro‐MMP‐2/TIMP‐2 complex). We have measured the binding of recombinant TIMP‐2 to intact HT‐1080 and MCF‐7 cells. HT‐1080 cells in suspension bound 125 I‐labeled rTIMP‐2 with a K d of 2.5 nM and 30,000 sites/cell. Monolayers of MCF‐7 cells were similarly found to bind [ 125 I]rTIMP‐2 with a K d of 1.6 nM and 25,000 sites/cell. Specific binding of MMP‐2 alone to HT‐1080 cells was not observed; however, pro‐MMP‐2/TIMP‐2 complex was capable of binding to the surface of HT‐1080 cells in a TIMP‐2‐dependent manner. Binding of rTIMP‐2 was not competed by the presence of TIMP‐1. These results suggest that rTIMP‐2 alone binds directly to the cell surface of HT‐1080 and MCF‐7 cell lines, and TIMP‐2 is capable of localizing MMP‐2 to the surface of HT‐1080 cells via interaction with a specific binding site.