The MMP/Cytokine Connection

The matrix metalloproteinases (MMPs) are members of a family of at least 20 proteolytic enzymes that contain a zinc ion at their active sites and can degrade collagen, elastins, and other components of the extracellular matrix (ECM). Cytokine activation of cells can lead to increased processing of MMPs from inactive zymogens to the active enzymes. Cytokines and their receptors can also be substrates for MMP action. Many of the membrane-bound cytokines, receptors, and adhesion molecules can be released from the cell surface by the action of a subset of metalloproteinases called convertases or adamalysins. This may be one mechanism for the down-regulation of cell surface receptors.

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References:

Nagase, H., and Woessner, J.F., Jr., Matrix metalloproteinases. J. Biol. Chem., 274, 21491-21494 (1999).

Rooprai, H.K., et al., The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells. Br. J. Cancer, 82, 52-55 (2000).

Stone, A.L., et al., Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review). J Protein Chem., 18, 447-465 (1999).

Killar, L., et al., Adamalysins. A family of metzincins including TNF-a converting enzyme (TACE). Ann. NY Acad. Sci., 878, 442-452 (1999).