Abstract
Background-Membrane-type matrix metalloproteinases (MT-MMPs) were initially identified as cell surface activators of MMP-2 (gelatinase A). We have reported that MTI-MMPs and MT3-MMPs are expressed by activated vascular smooth muscle cells (SMCs) and play a role in the regulation of cell function. Overexpression of MT-MMPs results in cell rounding, decreased adherence, and increased migration. Because integrin-mediated cell adhesion regulates these events, we have investigated the functional relationship between MT-MMPs and focal adhesion assembly. Methods and Results-Using adenoviral vectors we show that overexpression of MT-MMPs reduces the number of focal contacts, whereas the cell surface expression of integrin subunits remains unchanged. The 125-kDa focal adhesion kinase (FAK) is cleaved resulting in a 90-kDa fragment under these conditions, and paxillin is partially dissociated from FAK after its cleavage. Pretreatment of cells with BB94, a synthetic MMP inhibitor, rescues cell adhesion and prevents changes in focal adhesions, supporting a potential role for MT-MMP enzymatic activities. Conclusions-This study provides the first evidence that MT-MMPs are not only important in matrix degradation but also may affect the function of focal adhesions through FAK cleavage.
| Original language | English |
|---|---|
| Pages (from-to) | 839-844 |
| Number of pages | 6 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 24 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2004 |
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Keywords
- Cell adhesion
- Focal adhesion kinase
- Integrin
- MT1-MMP
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Cleavage of Focal Adhesion Kinase in Vascular Smooth Muscle Cells Overexpressing Membrane-Type Matrix Metalloproteinases. / Shofuda, Tomoko; Shofuda, Ken Ichi; Ferri, Nicola; Kenagy, Richard D.; Raines, Elaine W.; Clowes, Alexander W.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 5, 05.2004, p. 839-844.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cleavage of Focal Adhesion Kinase in Vascular Smooth Muscle Cells Overexpressing Membrane-Type Matrix Metalloproteinases
AU - Shofuda, Tomoko
AU - Shofuda, Ken Ichi
AU - Ferri, Nicola
AU - Kenagy, Richard D.
AU - Raines, Elaine W.
AU - Clowes, Alexander W.
PY - 2004/5
Y1 - 2004/5
N2 - Background-Membrane-type matrix metalloproteinases (MT-MMPs) were initially identified as cell surface activators of MMP-2 (gelatinase A). We have reported that MTI-MMPs and MT3-MMPs are expressed by activated vascular smooth muscle cells (SMCs) and play a role in the regulation of cell function. Overexpression of MT-MMPs results in cell rounding, decreased adherence, and increased migration. Because integrin-mediated cell adhesion regulates these events, we have investigated the functional relationship between MT-MMPs and focal adhesion assembly. Methods and Results-Using adenoviral vectors we show that overexpression of MT-MMPs reduces the number of focal contacts, whereas the cell surface expression of integrin subunits remains unchanged. The 125-kDa focal adhesion kinase (FAK) is cleaved resulting in a 90-kDa fragment under these conditions, and paxillin is partially dissociated from FAK after its cleavage. Pretreatment of cells with BB94, a synthetic MMP inhibitor, rescues cell adhesion and prevents changes in focal adhesions, supporting a potential role for MT-MMP enzymatic activities. Conclusions-This study provides the first evidence that MT-MMPs are not only important in matrix degradation but also may affect the function of focal adhesions through FAK cleavage.
AB - Background-Membrane-type matrix metalloproteinases (MT-MMPs) were initially identified as cell surface activators of MMP-2 (gelatinase A). We have reported that MTI-MMPs and MT3-MMPs are expressed by activated vascular smooth muscle cells (SMCs) and play a role in the regulation of cell function. Overexpression of MT-MMPs results in cell rounding, decreased adherence, and increased migration. Because integrin-mediated cell adhesion regulates these events, we have investigated the functional relationship between MT-MMPs and focal adhesion assembly. Methods and Results-Using adenoviral vectors we show that overexpression of MT-MMPs reduces the number of focal contacts, whereas the cell surface expression of integrin subunits remains unchanged. The 125-kDa focal adhesion kinase (FAK) is cleaved resulting in a 90-kDa fragment under these conditions, and paxillin is partially dissociated from FAK after its cleavage. Pretreatment of cells with BB94, a synthetic MMP inhibitor, rescues cell adhesion and prevents changes in focal adhesions, supporting a potential role for MT-MMP enzymatic activities. Conclusions-This study provides the first evidence that MT-MMPs are not only important in matrix degradation but also may affect the function of focal adhesions through FAK cleavage.
KW - Cell adhesion
KW - Focal adhesion kinase
KW - Integrin
KW - MT1-MMP
UR - http://www.scopus.com/inward/record.url?scp=2442506936&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442506936&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000126680.78500.4c
DO - 10.1161/01.ATV.0000126680.78500.4c
M3 - Article
C2 - 15044209
AN - SCOPUS:2442506936
VL - 24
SP - 839
EP - 844
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 5
ER -