{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:33:44Z","timestamp":1790757224355,"version":"4.1.0"},"reference-count":55,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2001,4,15]],"date-time":"2001-04-15T00:00:00Z","timestamp":987292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Integrin-mediated signals play an important but poorly understood role in regulating many leukocyte functions. In monocytes and monocytic leukemia cells, \u03b21 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 \u03b21 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 kB (NF-\u03baB) activation was then analyzed. We found that integrins activated both NF-\u03ba 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-kB activation. In contrast, a dominant negative mutant of Rac completely prevented NF-\u03ba B activation, but it did not affect MAPK activation. These results indicate that integrin signaling to NF-\u03ba 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-\u03ba 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-\u03ba B, while the other uses PI 3-K, MEK, and MAPK to activate other nuclear factors, such as Elk-1.<\/jats:p>","DOI":"10.1242\/jcs.114.8.1579","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T09:15:01Z","timestamp":1619255701000},"page":"1579-1589","source":"Crossref","is-referenced-by-count":40,"title":["Phosphatidylinositol 3-kinase mediates integrin-dependent NF-\u03baB and MAPK activation through separate signaling pathways"],"prefix":"10.1242","volume":"114","author":[{"given":"Merit","family":"Reyes-Reyes","sequence":"first","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 1 Immunology Department at Instituto de Investigaciones Biom\u00e9dicas , , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Mora","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 1 Immunology Department at Instituto de Investigaciones Biom\u00e9dicas , , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Zentella","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 2 Cell Biology Department at Instituto de Fisiolog\u00eda Celular , , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Rosales","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 1 Immunology Department at Instituto de Investigaciones Biom\u00e9dicas , , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2001,4,15]]},"reference":[{"key":"2024032023563213600_JOCES_114_8_1579C1","doi-asserted-by":"crossref","first-page":"18055","DOI":"10.1074\/jbc.274.25.18055","article-title":"Phosphoinositide 3-kinase-dependent and \u2212independent activation of the small GTPase Rac2 in human neutrophils","volume":"274","author":"Akasaki","year":"1999","journal-title":"J. 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