Phosphatidylinositol 3-kinase mediates integrin-dependent NF-?B and MAPK activation through separate signaling pathways
Por:
Reyes-Reyes M., Mora N., Zentella A., Rosales C.
Publicada:
1 ene 2001
Resumen:
Integrin-mediated signals play an important but poorly understood role in regulating many leukocyte functions. In monocytes and monocytic leukemia cells, ?1 integrin-mediated adhesion results in a strong induction of immediate-early genes that are important in inflammation. To investigate the signaling pathways from integrins in monocytic cells, THP-1 cells were stimulated via ?1 integrins by binding to fibronectin and by crosslinking the integrins with specific monoclonal antibodies. The involvement of MAPK and PI 3-K on nuclear factor ?B (NF-?B) activation was then analyzed. We found that integrins activated both NF-?B and MAPK in a PI 3-K-dependent manner, as wortmannin and LY294002 blocked these responses. However, the specific MEK inhibitor PD98059 did not prevent integrin-mediated NF-?B activation. In contrast, a dominant negative mutant of Rac completely prevented NF-?B activation, but it did not affect MAPK activation. These results indicate that integrin signaling to NF-?B is not mediated by the MAPK pathway, but rather by the small GTPase Rac. In addition, a dominant negative form of Rho augmented NF-?B activation and blocked MAPK activation, implying that these two pathways are in competition with each other. These data suggest that integrins activate different signaling pathways in monocytic cells. One uses PI 3-K and Rac to activate NF-?B, while the other uses PI 3-K, MEK, and MAPK to activate other nuclear factors, such as Elk-1.
Filiaciones:
Reyes-Reyes M.:
Immunology Department at Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Mora N.:
Immunology Department at Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Zentella A.:
Cell Biology Department at Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Rosales C.:
Immunology Department at Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
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