Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Sci. Signal., 8 July 2008
Vol. 1, Issue 27, p. re6
[DOI: 10.1126/scisignal.127re6]

REVIEWS

Tissue Inhibitors of Metalloproteinases in Cell Signaling: Metalloproteinase-Independent Biological Activities

William G. Stetler-Stevenson*

Chief, Extracellular Matrix Pathology Section, Cell and Cancer Biology Branch, Vascular Biology Faculty, Center for Cancer Research, National Cancer Institute (NCI), NIH, Advanced Technology Center, 8717 Grovemont Circle, Room 115, Bethesda, MD 20892–4605, USA.

Abstract: Over the past 20 years, the tissue inhibitors of metalloproteinases (TIMPs) have been implicated in direct regulation of cell growth and apoptosis. However, the mechanisms of these effects have been controversial. Recent work by several laboratories has identified specific signaling pathways and cell surface binding partners for members of the TIMP family. TIMP-2 binding to the integrin {alpha}3β1 is the first description of a cell surface receptor for a TIMP family member. TIMP-2 has been shown to induce gene expression, to promote G1 cell cycle arrest, and to inhibit cell migration. TIMP-1 binding to CD63 inhibits cell growth and apoptosis. These new findings suggest that TIMPs are multifunctional and can act either directly through cell surface receptors or indirectly through modulation of protease activity to direct cell fate. The emerging concept is that TIMPs function in a contextual fashion so that the mechanism of action depends on the tissue microenvironment.

*E-mail: sstevenw{at}mail.nih.gov

Citation: W. G. Stetler-Stevenson, Tissue Inhibitors of Metalloproteinases in Cell Signaling: Metalloproteinase-Independent Biological Activities. Sci. Signal. 1, re6 (2008).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Comparative Analysis of Novel Noninvasive Renal Biomarkers and Metabonomic Changes in a Rat Model of Gentamicin Nephrotoxicity.
M. Sieber, D. Hoffmann, M. Adler, V. S. Vaidya, M. Clement, J. V. Bonventre, N. Zidek, E. Rached, A. Amberg, J. J. Callanan, et al. (2009)
Toxicol. Sci. 109, 336-349
   Abstract »    Full Text »    PDF »
Breast Tumor Cells Transendothelial Migration Induces Endothelial Cell Anoikis Through Extracellular Matrix Degradation.
N. PEYRI, M. BERARD, F. FAUVEL-LAFEVE, V. TROCHON, B. ARBEILLE, H. LU, C. LEGRAND, and M. CREPIN (2009)
Anticancer Res 29, 2347-2355
   Abstract »    Full Text »    PDF »
Matrix metalloproteinase-9-mediated tissue injury overrides the protective effect of matrix metalloproteinase-2 during colitis.
P. Garg, M. Vijay-Kumar, L. Wang, A. T. Gewirtz, D. Merlin, and S. V. Sitaraman (2009)
Am J Physiol Gastrointest Liver Physiol 296, G175-G184
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882