Reactome | Activation of Matrix Metalloproteinases

Activation of Matrix Metalloproteinases

Stable Identifier

R-HSA-1592389

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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
19817485	Updated biological roles for matrix metalloproteinases and new "intracellular" substrates revealed by degradomics Butler, GS, Overall, CM	Biochemistry	2009
19616423	Matrix metalloproteinase proteomics: substrates, targets, and therapy Butler, GS, Overall, CM, Morrison, CJ, Rodríguez, D	Curr Opin Cell Biol	2009
19800373	Matrix metalloproteinases: what do they not do? New substrates and biological roles identified by murine models and proteomics Overall, CM, Morrison, CJ, Rodríguez, D	Biochim Biophys Acta	2010
17562450	The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases Opdenakker, G, Van den Steen, PE, Cauwe, B	Crit Rev Biochem Mol Biol	2007
	Matrix Metalloproteinases and TIMPs Woessner, J, Nagase, H		2000