Sci. STKE, 10 April 2001
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-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-B activation dependent on the activity of small guanosine triphosphatases (GTPases). One unexpected result was that NF-B activation was stimulated by the GTPase Rac and inhibited by the GTPase Rho. Thus, activation of an NF-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-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).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882