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Using a tuberin-deficient rat smooth muscle cell line, ELT3, we demonstrate that platelet-derived growth factor (PDGF) stimulates cell migration by 3.2-fold, whereas vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-\u03b1, and basic fibroblast growth factor (bFGF) increase migration by 2.1-, 2.1-, and 2.6-fold, respectively. Basal and PDGF-induced migration in tuberin-deficient ELT3, ELT4, and ERC15 cells was not significantly different from that of tuberin-positive transformed rat kidney epithelial 2, airway smooth muscle, and pulmonary arterial vascular smooth muscle cells. Expression of tuberin in tuberin-deficient ELT3 cells also had little effect on cell migration. In parallel experiments, the role of PI 3-kinase activation in ELT3 cell migration was investigated. LY-294002, a PI 3-kinase inhibitor, decreased PDGF-induced migration in a concentration-dependent manner with an IC<jats:sub>50<\/jats:sub>of \u223c5 \u03bcM. LY-294002 also abrogated ELT3 cell migration stimulated by bFGF and TGF-\u03b1 but not by VEGF and phorbol 12-myristate 13-acetate. Furthermore, transient expression of constitutively active PI 3-kinase (p110*) was sufficient to induce ELT3 cell migration. However, the migration induced by p110* was less than that induced by growth factors, suggesting other signaling pathways are also critically important in modulating growth factor-induced cell migration. These data suggest that PI 3-kinase is required for growth factor-induced cell migration and loss of tuberin appears to have little effect on cell migration.<\/jats:p>","DOI":"10.1152\/ajplung.00291.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:16:38Z","timestamp":1425413798000},"page":"L854-L862","source":"Crossref","is-referenced-by-count":32,"title":["Phosphatidylinositol 3-kinase but not tuberin is required for PDGF-induced cell migration"],"prefix":"10.1152","volume":"282","author":[{"given":"Carla","family":"Irani","sequence":"first","affiliation":[{"name":"Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena A.","family":"Goncharova","sequence":"additional","affiliation":[{"name":"Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah S.","family":"Hunter","sequence":"additional","affiliation":[{"name":"University of Texas M. 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