| First Author | Golubkov VS | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 51 | Pages | 42237-41 |
| PubMed ID | 16251193 | Mgi Jnum | J:105692 |
| Mgi Id | MGI:3616312 | Doi | 10.1074/jbc.M510139200 |
| Citation | Golubkov VS, et al. (2005) Centrosomal pericentrin is a direct cleavage target of membrane type-1 matrix metalloproteinase in humans but not in mice: potential implications for tumorigenesis. J Biol Chem 280(51):42237-41 |
| abstractText | Membrane type-1 matrix metalloproteinase (MT1-MMP) exhibits distinctive and important pericellular cleavage functions. Recently, we determined that MT1-MMP was trafficked to the centrosomes in the course of endocytosis. Our data suggested that the functionally important, integral, centrosomal protein, pericentrin-2, was a cleavage target of MT1-MMP in human and in canine cells and that the sequence of the cleavage sites were ALRRLLG1156 downward arrow L1157FG and ALRRLLS2068 downward arrow L2069FG, respectively. The presence of Asp-948 at the P1 position inactivated the corresponding site (ALRRLLD948-L949FGD) in murine pericentrin. To confirm that MT1-MMP itself cleaves pericentrin directly, rather than indirectly, we analyzed the cleavage of the peptides that span the MT1-MMP cleavage site. In addition, we analyzed glioma U251 cells, which co-expressed MT1-MMP with the wild type murine pericentrin and the D948G mutant. We determined that the D948G mutant that exhibited the cleavage sequence of human pericentrin was sensitive to MT1-MMP, whereas unmodified murine pericentrin was resistant to proteolysis. Taken together, our results confirm that MT1-MMP cleaves pericentrin-2 in humans but not in mice and that mouse models of cancer probably cannot be used to critically examine MT1-MMP functionality. |
