PathwayStep6020 PathwayStep6026 PathwayStep6025 PathwayStep6028 PathwayStep6027 PathwayStep6022 PathwayStep6021 PathwayStep6024 PathwayStep6023 PathwayStep6040 PathwayStep6042 PathwayStep6041 PathwayStep6044 PathwayStep6043 PathwayStep6046 PathwayStep6045 PathwayStep6031 PathwayStep6030 PathwayStep6035 PathwayStep6034 PathwayStep6033 PathwayStep6032 PathwayStep6039 PathwayStep6038 PathwayStep6037 PathwayStep6036 PathwayStep6029 Initial activation of proMMP1 Initial activation of proMMP3 MMP14:TIMP2 binds proMMP2 MMP14 (MT1-MMP) binds TIMP2 proMMP9 binds TIMP1 Full activation of MMP1 Autocatalytic activation of bound proMMP2 Autocatalytic activation of proMMP2 Initial activation of proMMP2 by MMP14 Initial activation of proMMP2 by MMP1, 7 Autocatalytic activation of MMP1 Autocatalytic activation of MMP7 Initial activation of proMMP7 by trypsin Initial activation of proMMP9 by MMPs Activation of proMMP8 Activation of proMMP9 by proteases Activation of MMP9 intermediate form by MMPs Activation of proMMP11 by FURIN Activation of proMMP10 Activation of proMMP7 by MMP3 Autocatalytic activation of MMP3 Initial activation of proMMP13 by plasmin and trypsin Initial activation of proMMP13 by MMP3 Initial activation of proMMP13 by MMP14 (MT1-MMP) Autocatalytic activation of proMMP13 Activation of MT-MMPs by FURIN MT-MMPs are sorted to the plasma membrane Activation of Matrix Metalloproteinases Authored: Jupe, S, 2011-09-09 Edited: Jupe, S, 2012-02-21 ISBN0 19 850268 0 Pubmed17562450 Pubmed19616423 Pubmed19800373 Pubmed19817485 Reactome Database ID Release 431592389 Reactome, http://www.reactome.org ReactomeREACT_118682 Reviewed: Butler, GS, 2012-02-28 Reviewed: Overall, CM, 2012-02-28 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.