scholarly journals The transmembrane domain is essential for the microtubular trafficking of membrane type-1 matrix metalloproteinase (MT1-MMP)

2005 ◽  
Vol 118 (21) ◽  
pp. 4975-4984 ◽  
Author(s):  
A. G. Remacle
Keyword(s):  
Matrix Metalloproteinase ◽  
Transmembrane Domain ◽  
Membrane Type

scholarly journals Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

2008 ◽  
Vol 19 (8) ◽  
pp. 3221-3233 ◽  
Author(s):  
Xiao-Yan Li ◽  
Ichiro Ota ◽  
Ikuo Yana ◽  
Farideh Sabeh ◽  
Stephen J. Weiss
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Cell Function ◽  
Catalytic Domain ◽  
Transmembrane Domain ◽  
Type I ◽  
Cell Trafficking ◽  
Membrane Type

Membrane type-1 matrix metalloproteinase (MT1-MMP) drives cell invasion through three-dimensional (3-D) extracellular matrix (ECM) barriers dominated by type I collagen or fibrin. Based largely on analyses of its impact on cell function under two-dimensional culture conditions, MT1-MMP is categorized as a multifunctional molecule with 1) a structurally distinct, N-terminal catalytic domain; 2) a C-terminal hemopexin domain that regulates substrate recognition as well as conformation; and 3) a type I transmembrane domain whose cytosolic tail controls protease trafficking and signaling cascades. The MT1-MMP domains that subserve cell trafficking through 3-D ECM barriers in vitro or in vivo, however, remain largely undefined. Herein, we demonstrate that collagen-invasive activity is not confined strictly to the catalytic, hemopexin, transmembrane, or cytosolic domain sequences of MT1-MMP. Indeed, even a secreted collagenase supports invasion when tethered to the cell surface in the absence of the MT1-MMP hemopexin, transmembrane, and cytosolic tail domains. By contrast, the ability of MT1-MMP to support fibrin-invasive activity diverges from collagenolytic potential, and alternatively, it requires the specific participation of MT-MMP catalytic and hemopexin domains. Hence, the tissue-invasive properties of MT1-MMP are unexpectedly embedded within distinct, but parsimonious, sequences that serve to tether the requisite matrix-degradative activity to the surface of migrating cells.

scholarly journals Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities

2004 ◽  
Vol 377 (3) ◽  
pp. 775-779 ◽  
Author(s):  
Douglas R. HURST ◽  
Martin A. SCHWARTZ ◽  
Mohammad A. GHAFFARI ◽  
Yonghao JIN ◽  
Harald TSCHESCHE ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Active Site ◽  
Catalytic Domain ◽  
Transmembrane Domain ◽  
Vital Role ◽  
Peptide Substrates ◽  
Enzyme Active Site ◽  
Membrane Type ◽  
Function Relationship

Membrane type 1-matrix metalloproteinase (MT1-MMP/MMP-14) is a major collagenolytic enzyme that plays a vital role in development and morphogenesis. To elucidate further the structure–function relationship between the human MT1-MMP active site and the influence of the haemopexin domain on catalysis, substrate specificity and inhibition kinetics of the cdMT1-MMP (catalytic domain of MT1-MMP) and the ecto domain ΔTM-MT1-MMP (transmembrane-domain-deleted MT1-MMP) were compared. For substrate 1 [Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2, where Mca stands for (7-methoxycoumarin-4-yl)acetyl- and Dpa for N-3-(2,4-dinitrophenyl)-l-2,3-diaminopropionyl], the activation energy Ea was determined to be 11.2 and 12.2 kcal/mol (1 cal=4.184 J) for cdMT1-MMP and ΔTM-MT1-MMP respectively, which is consistent with kcat/KM values of 7.37 and 1.46×104 M−1·s−1. The kcat/KM values for a series of similar single-stranded peptide substrates were determined and found to correlate with a slope of 0.17 for the two enzyme forms. A triple-helical peptide substrate was predicted to have a kcat/KM of 0.87×104 M−1·s−1 for ΔTM-MT1-MMP based on the value for cdMT1-MMP of 5.12×104 M−1·s−1; however, the actual value was determined to be 2.5-fold higher, i.e. 2.18×104 M−1·s−1. These results suggest that cdMT1-MMP is catalytically more efficient towards small peptide substrates than ΔTM-MT1-MMP and the haemopexin domain of MT1-MMP facilitates the hydrolysis of triple-helical substrates. Diastereomeric inhibitor pairs were utilized to probe further binding similarities at the active site. Ratios of Ki values for the inhibitor pairs were found to correlate between the enzyme forms with a slope of 1.03, suggesting that the haemopexin domain does not significantly modify the enzyme active-site structure.

scholarly journals Mutational and Structural Analyses of the Hinge Region of Membrane Type 1-Matrix Metalloproteinase and Enzyme Processing

2005 ◽  
Vol 280 (28) ◽  
pp. 26160-26168 ◽  
Author(s):  
Pamela Osenkowski ◽  
Samy O. Meroueh ◽  
Dumitru Pavel ◽  
Shahriar Mobashery ◽  
Rafael Fridman
Keyword(s):  
Matrix Metalloproteinase ◽  
Hinge Region ◽  
Membrane Type

4-Methylumbelliferone induces the expression of membrane type 1-matrix metalloproteinase in cultured human skin fibroblasts

2002 ◽  
Vol 298 (5) ◽  
pp. 646-650 ◽  
Author(s):  
Toshiya Nakamura ◽  
Takashi Ishikawa ◽  
Naoki Nanashima ◽  
Tomisato Miura ◽  
Hiroyuki Nozaka ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Human Skin ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Membrane Type

scholarly journals Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Sprouting Angiogenesis ◽  
Sphingosine 1 Phosphate ◽  
Wall Shear ◽  
Membrane Type

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.

scholarly journals Induction of membrane-type-1 matrix metalloproteinase by epidermal growth factor-mediated signaling in gliomas

2004 ◽  
Vol 6 (3) ◽  
pp. 188-199 ◽  
Author(s):  
Timothy E. Van Meter ◽  
William C. Broaddus ◽  
Harcharan K. Rooprai ◽  
Geoffrey J. Pilkington ◽  
Helen L. Fillmore
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Matrix Metalloproteinase ◽  
Epidermal Growth ◽  
Membrane Type
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