Activation of Matrix Metalloproteinases

Stable Identifier
R-HSA-1592389
Type
Pathway
Species
Homo sapiens
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Summation

The matrix metalloproteinases (MMPs), previously known as matrixins, are classically known to be involved in the turnover of extracellular matrix (ECM) components. However, recent high throughput proteomics analyses have revealed that ~80% of MMP substrates are non-ECM proteins including cytokines, growth factor binding protiens, and receptors. It is now clear that MMPs regulate ECM turnover not only by cleaving ECM components, but also by the regulation of cell signalling, and that some MMPs are beneficial and may be drug anti-targets. Thus, MMPs have important roles in many processes including embryo development, morphogenesis, tissue homeostasis and remodeling. They are implicated in several diseases such as arthritis, periodontitis, glomerulonephritis, atherosclerosis, tissue ulceration, and cancer cell invasion and metastasis. All MMPs are synthesized as preproenzymes. Alternate splice forms are known, leading to nuclear localization of select MMPs. Most are secreted from the cell, or in the case of membrane type (MT) MMPs become plasma membrane associated, as inactive proenzymes. Their subsequent activation is a key regulatory step, with requirements specific to MMP subtype.

Literature References
PubMed ID Title Journal Year
19616423 Matrix metalloproteinase proteomics: substrates, targets, and therapy

Morrison, CJ, Butler, GS, Rodríguez, D, Overall, CM

Curr Opin Cell Biol 2009
19817485 Updated biological roles for matrix metalloproteinases and new "intracellular" substrates revealed by degradomics

Butler, GS, Overall, CM

Biochemistry 2009
19800373 Matrix metalloproteinases: what do they not do? New substrates and biological roles identified by murine models and proteomics

Rodríguez, D, Morrison, CJ, Overall, CM

Biochim Biophys Acta 2010
17562450 The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases

Cauwe, B, Van den Steen, PE, Opdenakker, G

Crit Rev Biochem Mol Biol 2007
  Matrix Metalloproteinases and TIMPs

Woessner, J, Nagase, H

  2000
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