Abstract
Increasing evidence suggests that the cytoplasmic tail of membrane type 1 matrix metalloproteinase (MT1-MMP) is subject to phosphorylation and that this modification may influence its enzymatic activity at the cell surface. In this study, phosphorylated MT1-MMP is detected using a phospho-specific antibody recognizing a protein kinase C consensus sequence (phospho-TXR), and a MT1-MMP tail peptide is phosphorylated by exogenous protein kinase C. To characterize the potential role of cytoplasmic residue Thr567 in these processes, mutants that mimic a state of either constitutive (T567E) or defective phosphorylation (T567A) were expressed and analyzed for their functional effects on MT1-MMP activity and cellular behavior. Phospho-mimetic mutants of Thr567 exhibit enhanced matrix invasion as well as more extensive growth within a three-dimensional type I collagen matrix. Together, these findings suggest that MT1-MMP surface action is regulated by phosphorylation at cytoplasmic tail residue Thr567 and that this modification plays a critical role in processes that are linked to tumor progression.
Original language | English (US) |
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Pages (from-to) | 19791-19799 |
Number of pages | 9 |
Journal | Journal of Biological Chemistry |
Volume | 284 |
Issue number | 30 |
DOIs | |
State | Published - Jul 24 2009 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology