The Role of Membrane-Type 1 Matrix Metalloproteinase-Substrate Interactions in Pathogenesis

Int J Mol Sci. 2023 Jan 22;24(3):2183. doi: 10.3390/ijms24032183.

Abstract

A protease is an enzyme with a proteolytic activity that facilitates the digestion of its substrates. Membrane-type I matrix metalloproteinase (MT1-MMP), a member of the broader matrix metalloproteinases (MMP) family, is involved in the regulation of diverse cellular activities. MT1-MMP is a very well-known enzyme as an activator of pro-MMP-2 and two collagenases, MMP-8 and MMP-13, all of which are essential for cell migration. As an anchored membrane enzyme, MT1-MMP has the ability to interact with a diverse group of molecules, including proteins that are not part of the extracellular matrix (ECM). Therefore, MT1-MMP can regulate various cellular activities not only by changing the extra-cellular environment but also by regulating cell signaling. The presence of both intracellular and extra-cellular portions of MT1-MMP can allow it to interact with proteins on both sides of the cell membrane. Here, we reviewed the MT1-MMP substrates involved in disease pathogenesis.

Keywords: FGFRs; MMPs substrates; MT1-MMP; VEGFR-1; angiogenesis; proteolysis.

Publication types

  • Review

MeSH terms

  • Collagenases
  • Matrix Metalloproteinase 14*
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases* / metabolism
  • Proteins
  • Substrate Specificity

Substances

  • Collagenases
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Proteins