Linker region of Akt1/protein kinase Balpha mediates platelet-derived growth factor-induced translocation and cell migration.
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.
Kim
Eun Kyoung
EK
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.
Tucker
David F
DF
Yun
Sung Ji
SJ
Do
Kee Hun
KH
Kim
Min Sung
MS
Kim
Jae Ho
JH
Kim
Chi Dae
CD
Birnbaum
Morris J
MJ
Bae
Sun Sik
SS
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
D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020744:rac GTP-Binding Proteins