@article {tw5, editor = {,}, title = {Two Roads to the Nucleus}, volume = {2001}, number = {77}, pages = {tw5--tw5}, year = {2001}, doi = {10.1126/stke.2001.77.tw5}, publisher = {Science Signaling}, abstract = {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-κB 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-κB activation dependent on the activity of small guanosine triphosphatases (GTPases). One unexpected result was that NF-κB activation was stimulated by the GTPase Rac and inhibited by the GTPase Rho. Thus, activation of an NF-κB 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-κB and MAPK activation through separate signaling pathways. J. Cell Sci. 114, 1579-1598 (2001). [Online Journal]}, URL = {https://stke.sciencemag.org/content/2001/77/tw5}, eprint = {https://stke.sciencemag.org/content/2001/77/tw5}, journal = {Science Signaling} }