Modulation of the Membrane Type 1 Matrix Metalloproteinase Cytoplasmic Tail Enhances Tumor Cell Invasion and Proliferation in Three-dimensional Collagen Matrices*
AUTOR(ES)
Moss, Natalie M.
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
Increasing evidence suggests that the cytoplasmic tail of membrane type 1 matrix metalloproteinase (MT1-MMP) is subject to phos pho ryl a tion and that this modification may influence its enzymatic activity at the cell surface. In this study, phos pho ryl a ted 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 phos pho ryl a ted 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 phos pho ryl a tion (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 phos pho ryl a tion at cytoplasmic tail residue Thr567 and that this modification plays a critical role in processes that are linked to tumor progression.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2740404Documentos Relacionados
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