A role for FAK in the Concanavalin A-dependent secretion of matrix metalloproteinase-2 and -9.
To study the signaling pathway critical for the secretion of matrix metalloproteinases (MMPs), we examined the role of focal adhesion kinase (FAK) in Concanavalin A (Con A)-stimulated cells. We established a cell line in which FAK gene was conditionally inducible by use of FAK-null fibroblasts and the tetracycline repression system. In this cell line, FAK expression was undetectable in the presence of tetracycline but induced within 1 day by the removal of the drug. We found that FAK expression augmented the Con A-dependent secretion of MMP-9 and MMP-2. In contrast, proteolytic activation of MMP-2 by Con A-treatment did not require FAK expression. In addition, activation of MMP-secretion and tyrosine phosphorylation of FAK by Con A, but not the proteolytic activation of MMP-2, required attachment of the cells to the extracellular matrix. Taken together, our results suggest that the FAK signaling pathway play a pivotal role in the secretion of MMPs.
Sein
T T
TT
Laboratory of Molecular Pathogenesis, Nagoya University School of Medicine, Japan.
Thant
A A
AA
Hiraiwa
Y
Y
Amin
A R
AR
Sohara
Y
Y
Liu
Y
Y
Matsuda
S
S
Yamamoto
T
T
Hamaguchi
M
M
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology*; D004789:Enzyme Activation; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D014162:Transfection
D003208:Concanavalin A; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9