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.

Sci. STKE, 10 April 2001
Vol. 2001, Issue 77, p. tw5
[DOI: 10.1126/stke.2001.77.tw5]


Integrins Two Roads to the Nucleus

Integrins bind components of the extracellular matrix and then transduce information to the cell in a manner dependent on the cytoskeletal context inside the cell. Reyes-Reyes et al. show that integrin cross-linking in monocytic THP-1 cells can activate two separate pathways that regulate gene expression: an NF-{kappa}B pathway and a mitogen-activated protein kinase (MAPK) pathway. Both pathways required an intact cytoskeleton and the activity of phosphatidylinositol 3-kinase (PI3K). However, downstream of PI3K the pathways diverged with MAPK activation blocked by treatment with inhibitors of the MAPK activator MEK, and NF-{kappa}B activation dependent on the activity of small guanosine triphosphatases (GTPases). One unexpected result was that NF-{kappa}B activation was stimulated by the GTPase Rac and inhibited by the GTPase Rho. Thus, activation of an NF-{kappa}B reporter gene is greater in integrin-stimulated cells transfected with a dominant negative form of Rho or with an activated form of Rac. The balance of these competing GTPases may be an important regulatory input for integrin-mediated signaling.

M. Reyes-Reyes, N. Mora, A. Zentella, C. Rosales, Phosphatidylinositol 3-kinase mediates integrin-dependent NF-{kappa}B and MAPK activation through separate signaling pathways. J. Cell Sci. 114, 1579-1598 (2001). [Online Journal]

Citation: Two Roads to the Nucleus. Sci. STKE 2001, tw5 (2001).

To Advertise     Find Products

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