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TY - JOUR AU - Yoshii, Shigeto AU - Tanaka, Masamitsu AU - Otsuki, Yoshirou AU - Wang, Dong-Yu AU - Guo, Rong-Jun AU - Zhu, Yue AU - Takeda, Ririko AU - Hanai, Hiroyuki AU - Kaneko, Eizo AU - Sugimura, Haruhiko PY - 1999 DA - 1999/10/01 TI - αPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase JO - Oncogene SP - 5680 EP - 5690 VL - 18 IS - 41 AB - p21-activated kinase (PAK) is a common effector protein of the small GTPases Cdc42 and Rac, leading to the activation of downstream mitogen activated protein kinases. PAK also mediates polarized cytoskeletal changes induced by these GTPases. The recently identified PAK-interacting exchange factor (PIX) acts as a guanine nucleotide exchange factor on Rac, and colocalizes with PAK in a focal complex, but little is known about the associated signaling cascades, including upstream activators of PIX. In this study, we show that one of the isoforms of PIX, αPIX, is activated by signaling cascades from the platelet-derived growth factor (PDGF) receptor and EphB2 receptor, and from integrin-induced signaling through phosphatidylinositol 3-kinase (PI3-kinase). αPIX is activated by forming a complex with these receptors either via association with PAK and Nck, or direct association with the p85 regulatory subunit of PI3-kinase. Synthetic phosphoinositide and membrane targeted PI3-kinase augmented the αPIX activity in vivo. In Xenopus, aggregates of mesodermal cells derived from embryos microinjected with αPIX significantly increased the peripheral spreading on fibronectin substrate in response to PDGF through PI3-kinase. These results indicate that αPIX is activated by PI3-kinase, and is involved in the receptor mediated signaling leading to the activation of the kinase activity of PAK, and the migration of mesodermal cells on extracellular matrix. SN - 1476-5594 UR - https://doi.org/10.1038/sj.onc.1202936 DO - 10.1038/sj.onc.1202936 ID - Yoshii1999 ER -