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PMID: 19458085 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Modulation of the membrane type 1 matrix metalloproteinase cytoplasmic tail enhances tumor cell invasion and proliferation in three-dimensional collagen matrices.

The Journal of biological chemistry ·Vol. 284 ·No. 30 ·2009-07-24 ·Pages 19791-9

Moss NM, Wu YI, Liu Y, Munshi HG, Stack MS

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 Thr(567) 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 Thr(567) 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 Thr(567) and that this modification plays a critical role in processes that are linked to tumor progression.

MeSH Terms
Amino Acid Sequence Animals Breast Neoplasms/enzymology,genetics Carcinoma/enzymology,genetics Cell Line, Tumor Cell Movement Cell Proliferation Collagen Type I/chemistry,metabolism Cytoplasm/enzymology Humans Matrix Metalloproteinase 14/chemistry,genetics,metabolism Molecular Sequence Data Phosphorylation Point Mutation Rats Threonine/analysis,chemistry,genetics
Chemicals
Collagen Type I Threonine Matrix Metalloproteinase 14
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Moss Natalie M
Department of Cell and Molecular Biology, Northwestern University Feinberg Medical School, Chicago, Illinois 60611, USA.
Wu Yi I
Liu Yueying
Munshi H G
Stack M Sharon
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
Published
2009-07-24
Epub
2009-00-19
Pages
19791-9
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2740404
Subset
IM
Grants
NCI NIH HHS · R01 CA086984 · United States
NCI NIH HHS · R01 CA109545 · United States
NCI NIH HHS · R01 CA86984 · United States
NCI NIH HHS · CA86984-07S1 · United States
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