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J Biol Chem. 2010 May 21;285(21):15950-9. doi: 10.1074/jbc.M109.086447. Epub 2010 Mar 5.

Role of the netrin-like domain of procollagen C-proteinase enhancer-1 in the control of metalloproteinase activity.

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1
From the Institut de Biologie et Chimie des Protéines, CNRS/Université de Lyon UMR 5086, IFR128, 69367 Lyon, France.

Abstract

The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments.

PMID:
20207734
PMCID:
PMC2871463
DOI:
10.1074/jbc.M109.086447
[Indexed for MEDLINE]
Free PMC Article
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