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Cells 2018, 7(9), 117; https://doi.org/10.3390/cells7090117

Agonist-Biased Signaling via Matrix Metalloproteinase-9 Promotes Extracellular Matrix Remodeling

1
Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada
2
Department of Biology, Biosciences Complex, Queen’s University, Kingston, ON K7L 3N6, Canada
*
Author to whom correspondence should be addressed.
Received: 30 June 2018 / Revised: 12 August 2018 / Accepted: 23 August 2018 / Published: 26 August 2018
(This article belongs to the Special Issue Extracellular Matrix Remodeling)
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Abstract

The extracellular matrix (ECM) is a highly dynamic noncellular structure that is crucial for maintaining tissue architecture and homeostasis. The dynamic nature of the ECM undergoes constant remodeling in response to stressors, tissue needs, and biochemical signals that are mediated primarily by matrix metalloproteinases (MMPs), which work to degrade and build up the ECM. Research on MMP-9 has demonstrated that this proteinase exists on the cell surface of many cell types in complex with G protein-coupled receptors (GPCRs), and receptor tyrosine kinases (RTKs) or Toll-like receptors (TLRs). Through a novel yet ubiquitous signaling platform, MMP-9 is found to play a crucial role not only in the direct remodeling of the ECM but also in the transactivation of associated receptors to mediate and recruit additional remodeling proteins. Here, we summarize the role of MMP-9 as it exists in a tripartite complex on the cell surface and discuss how its association with each of the TrkA receptor, Toll-like receptors, epidermal growth factor receptor, and the insulin receptor contributes to various aspects of ECM remodeling. View Full-Text
Keywords: GPCR bias agonism; MMP-crosstalk; extracellular matrix; biased signaling; functional selectivity; insulin receptor; EGFR; Toll-like receptor; GPCR GPCR bias agonism; MMP-crosstalk; extracellular matrix; biased signaling; functional selectivity; insulin receptor; EGFR; Toll-like receptor; GPCR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Qorri, B.; Kalaydina, R.-V.; Velickovic, A.; Kaplya, Y.; Decarlo, A.; Szewczuk, M.R. Agonist-Biased Signaling via Matrix Metalloproteinase-9 Promotes Extracellular Matrix Remodeling. Cells 2018, 7, 117.

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