Table 1:
Enzyme | RECK | TIMP1 | TIMP2 | TIMP3 | TIMP4 |
---|---|---|---|---|---|
Substrates | MMP-(2,7,9,14,17), ADAMTS, ADAM10/17, EGFR, IL-6R, uPA | MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16 Low affinity for membrane type MMPs |
pro-MMP2, MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19. | MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15. Broadest inhibition spectrum, inhibits several members of the ADAM and ADAMTS families |
MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9. |
KO phenotype | • Embryonic lethality due to improper blood vessel maturation | • Increased ventricular remodeling • Altered ventricularstructure and function • Accelerated hepatocyte cell cycle • Increased resistance to corneal and pulmonary infection • Decreased adiposetissue weight on HFD • Impaired learning and memory |
• Motor defects and deficiency in prepulse inhibitor of the startle reflex | • Enlargement of airspace in lungs • Enhanced apoptosis during mammary gland involution • Excessive cardiac fibrosis • Increased TGFβ1and TNFα. • Increased risk of endotoxin shock • Unaltered tumorigenesis and angiogenesis |
• Reduced adipose tissue hypertrophy and fibrosis on a high fat diet. • Lower metabolic rate and energy expenditure. |
Role in Angiogene sis | • Negatively Regulates | • Negatively Regulates | • Negatively Regulates • Enhances expression of RECK by interacting with α3β1 integrin switching signaling from Rac 1 to Rap 1 |
• NegativelyRegulates • Binds VEGFR2 to block VEGF signaling on endothelial cells. • Binds AT2R |
• Negatively Regulates |
Role in Cell Migration | • Inhibitsendothelial cell migration • SuppressesSMC proliferation and migration |
• Increases lungcancer cell migration • Increases hepatoma cell migration • Increases cancer associated fibroblasts migration • Decreases microvascular endothelial cell migration |
• Inhibits cancercell migration • Inhibitsmacrophage migration to atherosclerotic plaques |
• Suppresses SMC proliferation and migration | • Inhibits SMCs migration |
Role in Proliferation | • Anti-proliferative | • Promotes growth ofkeratinocytes and fibroblasts • Increases Ras-GTP • Inhibits caspase mediated apoptosis |
• Potentiates erythroid activity and cell growth in metanephric mesenchyme cells • Increases amount of Ras-GTP • Reduces apoptosis |
• Promotes apoptosis in a number of cancer cell lines and rat vascular smooth muscle cells | • Induces aortic SMC apoptosis |
Structure | • Rich incysteine residues • 971 residues • 110kDa • 6 disulfidebonds (Kazal motif) • 5 asparagine glycosylation sites |
• Conserved cysteineresidues • 207 residues • 25kDa • 6 disulfide bonds (NTR module) • 2 asparagine glycosylation sites |
• Conserved cysteine residues • 220 residues • 25kDa • 6 disulfide bonds (NTR module) |
• Conserved cysteineresidues • 211 residues • 25kDa • 6 disulfide bonds (NTR module) |
• Conserved cysteine residues • 224 residues • 25kDa • 6 disulfidebonds (NTR module) |