Human membrane type-2 matrix metalloproteinase is defective in cell-associated activation of progelatinase A.
Transfection of the mouse membrane type-2 matrix metalloproteinase (MT2-MMP) gene into COS-1 cells resulted in activation of progelatinase A; however, that of the human gene had no effect. Expression of human and mouse MT2-MMP chimeric proteins revealed the defect of human MT2-MMP which resides in the region between amino acid (aa) residues 155 and 271. Seven aa residues in this region were not conserved between human and mouse MT2-MMP. Substitution with the corresponding mouse residue, proline-183 to serine and glutamine-185 to aspartic acid, recovered cell-associated progelatinase A activation function. These residues are located in the insertion sequence-2 (IS-2), which was conserved in six clones of the human MT2-MMP gene from different sources, except that of proline-183 which was substituted with serine from HT1080 cells. These results indicate that human MT2-MMP is defective in cell-associated activation of progelatinase A, and this is attributed to IS-2. These findings emphasize the importance of IS-2 in MT2-MMP functionality.
Miyamori
H
H
Department of Molecular Virology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan.
Takino
T
T
Seiki
M
M
Sato
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology; D004251:DNA Transposable Elements; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D000911:Antibodies, Monoclonal; D004251:DNA Transposable Elements; D004792:Enzyme Precursors; C507098:MMP15 protein, human; C507100:Mmp15 protein, mouse; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D018093:Gelatinases; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase