Cell Surface-mediated Activation of Progelatinase A: Demonstration of the Involvement of the C-terminal Domain of Progelatinase A in Cell Surface Binding and Activation of Progelatinase A by Primary Fibroblasts

Overview

Journal Biochem J

Specialty Biochemistry

Date 1994 Nov 15

PMID 7998943

Citations 12

Authors

R V WARD

S J Atkinson

J J Reynolds

G Murphy

Affiliations

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Abstract

We report that the isolated C-terminal domain of progelatinase A is inhibitory to the activation of this proenzyme by primary skin fibroblast plasma membranes but is unable to inhibit organomercurial-induced self-cleavage and activation. Ligand binding studies demonstrate that fibroblasts stimulated with concanavalin A to activate progelatinase A have a significantly enhanced level of cell surface-associated progelatinase A. Tissue inhibitor of metalloproteinases-2 (TIMP-2), an effective inhibitor of membrane-mediated progelatinase A activation, is able to abolish the enhanced level of cell surface-associated progelatinase A that occurs following stimulation. TIMP-1, a poor inhibitor of membrane activation, is unable to inhibit the cell surface binding of progelatinase A. The enhancement in the binding of 125I-progelatinase A to fibroblasts following concanavalin A stimulation can be blocked by the inclusion of excess C-terminal gelatinase A but not by a truncated form of gelatinase A lacking the C-terminal domain. Scatchard analysis of the binding of 125I-progelatinase A to concanavalin A-stimulated fibroblasts has identified 950,000 gelatinase binding sites per cell with a Kd of 1.3 x 10(-8) M. Analysis of non-stimulated fibroblasts has identified 500,000 sites per cell with a Kd of 2.6 x 10(-8) M. We propose that membrane-mediated activation of progelatinase A involves binding of the proenzyme through its C-terminal domain to the cell surface and that TIMP-2 can inhibit activation by interaction with progelatinase A through the C-terminal domain, thus preventing binding of the proenzyme.

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References

McPherson G . Analysis of radioligand binding experiments. A collection of computer programs for the IBM PC. J Pharmacol Methods. 1985; 14(3):213-28. DOI: 10.1016/0160-5402(85)90034-8. View

Murphy G, McAlpine C, Poll C, Reynolds J . Purification and characterization of a bone metalloproteinase that degrades gelatin and types IV and V collagen. Biochim Biophys Acta. 1985; 831(1):49-58. DOI: 10.1016/0167-4838(85)90148-7. View

Collier I, Wilhelm S, Eisen A, Marmer B, Grant G, Seltzer J . H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem. 1988; 263(14):6579-87. View

Stetler-Stevenson W, Krutzsch H, Wacher M, Margulies I, Liotta L . The activation of human type IV collagenase proenzyme. Sequence identification of the major conversion product following organomercurial activation. J Biol Chem. 1989; 264(3):1353-6. View

Docherty A, Murphy G . The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. Ann Rheum Dis. 1990; 49 Suppl 1:469-79. View

Brown P, Levy A, Margulies I, Liotta L, Stetler-Stevenson W . Independent expression and cellular processing of Mr 72,000 type IV collagenase and interstitial collagenase in human tumorigenic cell lines. Cancer Res. 1990; 50(19):6184-91. View

Overall C, Sodek J . Concanavalin A produces a matrix-degradative phenotype in human fibroblasts. Induction and endogenous activation of collagenase, 72-kDa gelatinase, and Pump-1 is accompanied by the suppression of the tissue inhibitor of matrix metalloproteinases. J Biol Chem. 1990; 265(34):21141-51. View

Okada Y, Morodomi T, Enghild J, Suzuki K, Yasui A, Nakanishi I . Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymic properties. Eur J Biochem. 1990; 194(3):721-30. DOI: 10.1111/j.1432-1033.1990.tb19462.x. View

Senior R, Griffin G, Fliszar C, Shapiro S, Goldberg G, Welgus H . Human 92- and 72-kilodalton type IV collagenases are elastases. J Biol Chem. 1991; 266(12):7870-5. View

10.

Stetler-Stevenson W . Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 1990; 9(4):289-303. DOI: 10.1007/BF00049520. View

11.

Howard E, Bullen E, Banda M . Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem. 1991; 266(20):13064-9. View

12.

Murphy G, Cockett M, WARD R, Docherty A . Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. A quantitative comparison of the activities of 95 kDa and 72 kDa gelatinases, stromelysins-1 and -2 and punctuated metalloproteinase (PUMP). Biochem J. 1991; 277 ( Pt 1):277-9. PMC: 1151220. DOI: 10.1042/bj2770277. View

13.

Yamagata S, Yoshii Y, Suh J, Tanaka R, Shimizu S . Occurrence of an active form of gelatinase in human gastric and colorectal carcinoma tissues. Cancer Lett. 1991; 59(1):51-5. DOI: 10.1016/0304-3835(91)90135-5. View

14.

WARD R, Hembry R, Reynolds J, Murphy G . The purification of tissue inhibitor of metalloproteinases-2 from its 72 kDa progelatinase complex. Demonstration of the biochemical similarities of tissue inhibitor of metalloproteinases-2 and tissue inhibitor of metalloproteinases-1. Biochem J. 1991; 278 ( Pt 1):179-87. PMC: 1151465. DOI: 10.1042/bj2780179. View

15.

WARD R, Atkinson S, Slocombe P, Docherty A, Reynolds J, Murphy G . Tissue inhibitor of metalloproteinases-2 inhibits the activation of 72 kDa progelatinase by fibroblast membranes. Biochim Biophys Acta. 1991; 1079(2):242-6. DOI: 10.1016/0167-4838(91)90132-j. View

16.

Matsubara M, Girard M, Kublin C, Cintron C, Fini M . Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodelling cornea. Dev Biol. 1991; 147(2):425-39. DOI: 10.1016/0012-1606(91)90300-r. View

17.

Howard E, Banda M . Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites on human 72-kDa gelatinase. Identification of a stabilization site. J Biol Chem. 1991; 266(27):17972-7. View

18.

Nagase H, Ogata Y, Suzuki K, Enghild J, Salvesen G . Substrate specificities and activation mechanisms of matrix metalloproteinases. Biochem Soc Trans. 1991; 19(3):715-8. DOI: 10.1042/bst0190715. View

19.

Murphy G, Willenbrock F, WARD R, Cockett M, Eaton D, Docherty A . The C-terminal domain of 72 kDa gelatinase A is not required for catalysis, but is essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases. Biochem J. 1992; 283 ( Pt 3):637-41. PMC: 1130931. DOI: 10.1042/bj2830637. View

20.

Fridman R, Fuerst T, Bird R, Hoyhtya M, Oelkuct M, Kraus S . Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions. J Biol Chem. 1992; 267(22):15398-405. View