"Expression of CA-PI3K caused a significant increase in membrane-associated Tiam1 (Fig. 5B), whereas expression of DN-PI3K caused increased cytosolic Tiam1 (Fig. 5A). CS did not affect the distribution of Tiam1 when either CA-PI3K or DN-PI3K was expressed. We also found that treatment with the Tiam1 inhibitor NSC23766 caused increased cytosolic localization of Tiam1, decreased Rac1 activity, and decreased cell migration"
"Phosphatidylinositol 3-kinase (PI3K) is recruited to the membrane by intact E-cadherin adhesion junctions, where it generates phosphatidylinositol-(3,4,5)- triphosphate (PIP3), resulting in the activation of the RHO-GEF TIAM1 and subsequently of RAC1 and CDC42."
"Moreover, in 1321N1 astrocytoma cells, translocation of Tiam1 to the cytosol, following receptor-mediated stimulation of PtdIns(4,5)P(2) breakdown, correlates with decreased Rac1-GTP levels, indicating that membrane-association is required for GDP/GTP exchange on Rac1."