Figure 5.

Interconnectivity within TIMP2 targets.

The TIMP2 interactome displays extensive interactions with each other, largely mediated through components of the extracellular matrix (ECM). MMPs (soluble and membrane-type (MT-MMPs)) and ADAM12 are major mediators of ECM proteolysis, events that modulate all aspects of tissue biology. Cleaved ECM components are endocytosed and degraded largely via LRP1, an event that likely involves co-operation with β1 integrins (not shown). The LRP1 - β1 integrin relationship is complex and incompletely understood, since LRP1 can promote integrin maturation and transport (159) yet also mediate endocytosis of mature β1 integrin (159,160). MT-MMPs and ADAM12 display sheddase activity against LRP1, mediating the release of soluble LRP1 molecules that successfully prevent target endocytosis. Additionally, membrane-type MMP14 has been shown to associated with α3β1 integrin via CD151 that inhibits MMP14s proteinase activity. Integrins are the major membrane proteins that integrate the extracellular matrix and cytoskeleton. Created with BioRender.com.