Analysis of the effects of Tissue Inhibitor of Metalloproteinases-1, -2 and -3 N- and C-terminal domains on signaling markers during X. laevis development

Sashko Damjanovski


Extracellular matrix (ECM) remodeling is accomplished largely by matrix metalloproteinases (MMPs), which cleave individual components of the ECM to facilitate cell migration. Tissue inhibitors of metalloproteinases (TIMPs) are secreted MMP inhibitors, which, along with the cell surface MMP inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK), bind to MMPs and inhibit their activity. Although TIMPs were originally characterized based on their MMP-inhibitory activities, TIMPs are now known to be multifunctional proteins, with structurally and functionally distinct N- and C-terminal domains. TIMP N-terminal domains bind to and inhibit MMPs, while their C-terminal domains have demonstrated in vitro cell signaling activity in apoptosis, cell proliferation, and cell migration pathways.  This study utilized TIMP N- and C-terminal domain constructs to examine individual domain functions related to cell proliferation, apoptosis and migration in Xenopus laevis embryos. Western blot analysis revealed that none of the TIMP constructs altered phospho-histone-3 levels. Conversely, TIMP-1 full-length and C-terminal domain constructs both elevated caspase-3 and RECK levels, while TIMP-2 C-terminal and TIMP-3 N-terminal domain constructs both decreased RECK levels. Thus the C-terminal domains of Xenopus TIMP-1 and -2, but not TIMP-3, can transduce signals that are independent of their MMP inhibitory role.


TIMP, Xenopus laevis, RECK, apoptosis

Full Text:


Comments on this article

View all comments

This website is optimized for the last versions of Internet Explorer (V. 7 or higher) and Firefox. We therefore advise to download (or upgrade your internet browser to) IE 7 or Firefox. All rights reserved to The All Results Journals (c).

To help promote The All Results Journals:Biol (ISSN:2172-4784) you can now download our poster and display it in your library, common room, office or laboratory.