Domain Interactions in the Gelatinase A·TIMP-2·MT1-MMP Activation Complex

Overall, Christopher M.; Tam, Eric; McQuibban, G. Angus; Morrison, Chet A.; Wallon, U. Margaretha; Bigg, Heather F.; King, Ae; Roberts, Clive J.

doi:10.1074/jbc.m005932200

Cited by 86 publications

(58 citation statements)

References 49 publications

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“…Three mechanisms for proMMP-2 activation have been described at this moment; autocatalytical activation, TIMP-2 dependent activation and cell-surface associated urokinase-type plasminogen activator (uPA)/plasmin system dependent activation [34][35][36][37][38][39][40]. The mechanisms differ substantially, but have a characteristic phenomenon.…”

Section: Activation Of Mmpsmentioning

confidence: 99%

The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

Klein

Vellenga

Fraaije

et al. 2004

Critical Reviews in Oncology/Hematology

312

170

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Section: Activation Of Mmpsmentioning

confidence: 99%

The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

Klein

Vellenga

Fraaije

et al. 2004

Critical Reviews in Oncology/Hematology

312

170

View full text Add to dashboard Cite

“…The fixed cultures were incubated overnight at 4°C in Tris-buffered saline (TBS) (150 mM NaCl, 20 mM Tris, pH 7.5) containing 2% bovine serum albumin (BSA) (TBS-BSA) and 10% normal goat serum (Molecular Probes). Designated wells were incubated with 2.5 g/ml mouse monoclonal antibody against hMT1-MMP (MAB918) (R & D Systems, Inc.), 2.5 g/ml rabbit polyclonal antibody against MT1-MMP (AB815) (Chemicon), 20 g/ml mouse monoclonal antibody against MT2-MMP (MAB3220) (Chemicon), 2.5 g/ml affinity-purified rabbit polyclonal antibodies that we raised against the following peptide sequences in hMT2-MMP, , using methods described before (21), control mouse immunoglobulin (Dako), control non-immune rabbit serum (Molecular Probes), or TBS-BSA alone, for 2 h at 20°C and then washed four times with excess TBS. Texas Red-conjugated goat anti-mouse IgG or anti-rabbit IgG antiserum (Molecular Probes) diluted in TBS-BSA to 1%, was added to appropriate samples.…”

Section: Methodsmentioning

confidence: 99%

“…Texas Red-conjugated goat anti-mouse IgG or anti-rabbit IgG antiserum (Molecular Probes) diluted in TBS-BSA to 1%, was added to appropriate samples. Secondary antibodies were highly pre-absorbed against other species' IgG by the supplier and further screened in our laboratory, in pilot experiments, to verify lack of nonspecific binding to cultured cells as described (21). The cells were washed four times in TBS and incubated in 10 M Hoechst 33342 in TBS for 10 min, then washed again four times in TBS.…”

Section: Methodsmentioning

confidence: 99%

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Cellular Activation of MMP-2 (Gelatinase A) by MT2-MMP Occurs via a TIMP-2-independent Pathway

Morrison¹,

Butler²,

Bigg³

et al. 2001

Journal of Biological Chemistry

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159

142

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“…1a). Earlier, it has been shown that TIMP-2 regulates the amount of active 60-kDa MT1-MMP enzyme on the cell surface, whereas in the absence of TIMP-2 MT1-MMP undergoes autocatalysis to the 42-kDa form (41,42). Apparently, our immunoprecipitation experiments showing high levels of the 42-kDa form point to an insufficiency of TIMP-2 relative to MT1-MMP in HT-MT transfectants (43).…”

Section: Ttg Is Degraded and Inactivated On The Surface Of Cancermentioning

confidence: 99%

Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and Locomotion

Belkin

Akimov²,

Zaritskaya

et al. 2001

Journal of Biological Chemistry

224

206

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Cell invasion requires cooperation between adhesion receptors and matrix metalloproteinases (MMPs). Remodeling of the extracellular matrix (ECM)1 is critical for cancer cell invasion and tumorigenesis (1-5). Membrane type matrix metalloproteinases (MT-MMPs) localized to the invasive front of highly motile cancer cells (6, 7) were shown to be directly involved in matrix breakdown (8 -13). A cooperation involving MT-MMPs and cell adhesion receptors is likely to be essential to migrating cells (3, 14 -16). So far, six members of the MT-MMP subfamily have been identified and partially characterized (2, 17-22). MT1-, MT2-, and MT3-MMP strongly contribute to tumor cell invasion (12). Recent studies demonstrated a functional significance and a direct role of MT1-, MT2-, and MT3-MMP in cell locomotion on laminin-5 (11) and three-dimensional collagen type I lattice (8, 9, 12). In addition, MT-MMPs contribute indirectly to cell invasion by activating soluble secretory MMP-2 (23) and MMP-13 (24), which further cleave multiple matrix substrates (2, 5, 25-29).Integrin adhesion receptors dynamically regulate cell-matrix interactions by the binding to matrix proteins and inside-out signaling (30,31). This allows cells to discriminate any subtle alteration of the environment and to adjust cell locomotion accordingly. Direct interactions with multiple transmembrane and cell surface proteins (32) including integrin-associated protein-50 (33), TM4SF proteins (tetraspanins) (34) and tTG (35) further attenuate adhesive and signaling efficiency of integrins.Cell surface tTG (protein-glutamine ␥-glutamyltransferase, EC 2.3.2.13) promotes integrin-dependent adhesion and spreading of cells. By both direct associations with multiple ␤ 1 and ␤ 3 integrins and the binding with Fn, tTG independently mediates the interactions of integrins with Fn (35). The high affinity binding of tTG with Fn specifically involves the 42 kDa gelatin-binding domain of the Fn molecule, which consists of modules I 6 II 1,2 I 7-9 (36). The enhancement of integrin-mediated adhesion and spreading of cells on Fn is independent from the enzymatic activity of surface tTG (35). Intriguingly, reduced expression of tTG has been linked to aggressiveness and high metastatic potential of tumors, whereas overexpression of tTG in fibrosarcomas inhibited primary tumor growth (37, 38). Proteolysis of tTG at the normal tissue/tumor boundary was observed in invasive tumors (38).Here, we report that depending on the structure of the ECM, MT-MMPs are capable of both positively and negatively regulating locomotion of cancer cells. Matrix-dependent proteolysis of surface tTG by MT1-MMP occurs on tumor cells of a diverse tissue origin, thereby representing a general phenomenon and a novel MT-MMP function. Our data suggest an existence of an unexpected link between tumor cell locomotion, the ECM and membrane-anchored MMPs. Regulatory proteolysis of cell surface adhesion proteins by the adjacent MT-MMP molecules is likely to play a significant functional role in cancer cell invasion.

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Domain Interactions in the Gelatinase A·TIMP-2·MT1-MMP Activation Complex

Cited by 86 publications

References 49 publications

The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

Cellular Activation of MMP-2 (Gelatinase A) by MT2-MMP Occurs via a TIMP-2-independent Pathway

Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and Locomotion

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