Table 1 Functional properties of the tissue inhibitors of metalloproteinases (TIMPs) (based on reviews [1-4])
Property | TIMP-1 | TIMP-2 | TIMP-3 | TIMP-4 |
|---|---|---|---|---|
Approximate protein size | 28 kDa | 21 kDa | 24/27 kDa | 22 kDa |
Localisation | Soluble | Soluble + cell surface | Extracellular matrix | Cell surface, tissue-specific |
Intracellular activation | Receptor(s) Nuclear translocation | Receptor(s) | No | Not known |
Proteinase type inhibition | Secreted MMP, ADAMTS | Secreted MMP, MT-MMP | MT-MMP, ADAMTS | Secreted MMP, MT-MMP |
Apoptosis | Inhibits (BCL-2 regulation) | Inhibits | Promotes (TACE, death receptors) | Promotes |
Angiogenesis | Inhibits | Inhibits | Inhibits | Inhibits |
Proliferation | Stimulates | Stimulates | Inhibits | Stimulates |
Tumour growth | Promotes | Promotes | Inhibits | Not known |
Knockout mice | Resistance to Pseudomonas infection | Impaired pro-MMP2 activation | Lung emphysema, chronic hepatitis. High TNF-α | Not known |