The inactive 44-kDa processed form of membrane type 1 matrix metalloproteinase (MT1-MMP) enhances proteolytic activity via regulation of endocytosis of active MT1-MMP

被引:26
作者
Cho, Jin-Ah [1 ,2 ]
Osenkowski, Pamela [1 ,2 ]
Zhao, Huiren [1 ,2 ]
Kim, Seaho [1 ,2 ]
Toth, Marta [1 ,2 ]
Cole, Kristina [1 ,2 ]
Aboukameel, Amro [1 ,2 ]
Saliganan, Allen [1 ,2 ]
Schuger, Lucia [1 ,2 ]
Bonfil, R. Daniel [1 ,2 ]
Fridman, Rafael [1 ,2 ]
机构
[1] Wayne State Univ, Sch Med, Dept Pathol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA
[2] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Proteases & Canc Program, Detroit, MI 48201 USA
关键词
D O I
10.1074/jbc.M708943200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Membrane type 1 (MT1) matrix metalloproteinase (MMP-14) is a membrane-tethered MMP considered to be a major mediator of pericellular proteolysis. MT1-MMP is regulated by a complex array of mechanisms, including processing and endocytosis that determine the pool of active proteases on the plasma membrane. Autocatalytic processing of active MT1-MMP generates an inactive membrane-tethered 44-kDa product (44-MT1) lacking the catalytic domain. This form preserves all other enzyme domains and is retained at the cell surface. Paradoxically, accumulation of the 44-kDa form has been associated with increased enzymatic activity. Here we report that expression of a recombinant 44-MT1 (Gly(285)-Val(582)) in HT1080 fibrosarcoma cells results in enhanced pro-MMP-2 activation, proliferation within a three-dimensional collagen I matrix, and tumor growth and lung metastasis in mice. Stimulation of pro-MMP-2 activation and growth in collagen I was also observed in other cell systems. Expression of 44-MT1 in HT1080 cells is associated with a delay in the rate of active MT1-MMP endocytosis resulting in higher levels of active enzyme at the cell surface. Consistently, deletion of the cytosolic domain obliterates the stimulatory effects of 44-MT1 on MT1-MMP activity. In contrast, deletion of the hinge turns the 44-MT1 form into a negative regulator of enzyme function in vitro and in vivo, suggesting a key role for the hinge region in the functional relationship between active and processed MT1-MMP. Together, these results suggest a novel role for the 44-kDa form of MT1-MMP generated during autocatalytic processing in maintaining the pool of active enzyme at the cell surface.
引用
收藏
页码:17391 / 17405
页数:15
相关论文
共 85 条
  • [51] Protein targeting by tyrosine- and di-leucine-based signals: Evidence for distinct saturable components
    Marks, MS
    Woodruff, L
    Ohno, H
    Bonifacino, JS
    [J]. JOURNAL OF CELL BIOLOGY, 1996, 135 (02) : 341 - 354
  • [52] Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK1/2-and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-β1-induced pericellular collagenolysis
    Munshi, HG
    Wu, YI
    Mukhopadhyay, S
    Ottaviano, AJ
    Sassano, A
    Koblinski, JE
    Platanias, LC
    Stack, MS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (37) : 39042 - 39050
  • [53] Calcium regulation of matrix metalloproteinase-mediated migration in oral squamous cell carcinoma cells
    Munshi, HG
    Wu, YI
    Ariztia, EV
    Stack, MS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (44) : 41480 - 41488
  • [54] Structure and function of matrix metalloproteinases and TIMPs
    Nagase, H
    Visse, R
    Murphy, G
    [J]. CARDIOVASCULAR RESEARCH, 2006, 69 (03) : 562 - 573
  • [55] Competitive disruption of the tumor-promoting function of membrane type 1 matrix metalloproteinase/matrix metalloproteinase-14 in vivo
    Nonaka, T
    Nishibashi, K
    Itoh, Y
    Yana, I
    Seiki, M
    [J]. MOLECULAR CANCER THERAPEUTICS, 2005, 4 (08) : 1157 - 1166
  • [56] Kinetic analysis of the binding of human matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2
    Olson, MW
    Gervasi, DC
    Mobashery, S
    Fridman, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (47) : 29975 - 29983
  • [57] Mutational and structural analyses of the hinge region of membrane type 1-matrix metalloproteinase and enzyme processing
    Osenkowski, P
    Meroueh, SO
    Pavel, D
    Mobashery, S
    Fridman, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) : 26160 - 26168
  • [58] Processing, shedding, and endocytosis of membrane type 1-matrix metalloproteinase (MT1-MMP)
    Osenkowski, P
    Toth, M
    Fridman, R
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2004, 200 (01) : 2 - 10
  • [59] Matrix metalloproteinase-2 activation in human hepatic fibrosis regulation by cell-matrix interactions
    Préaux, AM
    Mallat, A
    Van Nhieu, JT
    d'Ortho, MP
    Hembry, RM
    Mavier, P
    [J]. HEPATOLOGY, 1999, 30 (04) : 944 - 950
  • [60] An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase
    Ratnikov, BI
    Rozanov, DV
    Postnova, TI
    Baciu, PG
    Zhang, H
    DiScipio, RG
    Chestukhina, GG
    Smith, JW
    Deryugina, EI
    Strongin, AY
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (09) : 7377 - 7385