title: Linker region of Akt1/protein kinase Balpha mediates platelet-derived growth factor-induced translocation and cell migration.
abstract: The phosphatidylinositol 3-kinase (PI3K) signaling pathway(s) is activated by a variety of agonists to regulate cell migration. Here, we show that the stimulation of mouse embryonic fibroblasts with platelet-derived growth factor (PDGF) induces migration in a PI3K-dependent manner. Cells lacking Akt1/PKBalpha exhibit impaired migration and peripheral ruffling in response to PDGF stimulation, whereas cells lacking Akt2/PKBbeta are normal. In addition, over-expression of Akt1/PKBalpha but not Akt2/PKBbeta is sufficient to restore PDGF-induced cell migration in an Akt1/PKBalpha and Akt2/PKBbeta deficient background. In response to PDGF stimulation, Akt1/PKBalpha selectively translocates to membrane ruffles, however, this localization is abrogated by substituting the linker region of Akt2/PKBbeta. Similarly, expression of an Akt2/PKBalpha chimera containing the linker region of Akt1/PKBalpha restored PDGF-induced migration in cells lacking both Akt1/PKBalpha and Akt2/PKBbeta. Finally, over-expression of constitutively active Rac rescues PDGF-induced migration defects in cells lacking Akt1/PKBalpha. Given these results, we suggest that Akt1/PKBalpha controls cell migration by selectively translocating to the leading edge and activating Rac.
authors.affiliation: MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, School of Medicine, Pusan National University, Ami-dong 1-ga 10, Seo-gu, Pusan 602-739, Republic of Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.forename: David F
authors.initials: DF
authors.lastname: Tucker
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Yun
authors.forename: Kee Hun
authors.initials: KH
authors.lastname: Do
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Birnbaum
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000201:enzymology; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020744:rac GTP-Binding Proteins