Literature DB >> 18779657

Lysophosphatidic acid induces cell migration through the selective activation of Akt1.

Eun Kyoung Kim1, Sung Ji Yun, Kee Hun Do, Min Sung Kim, Mong Cho, Dong-Soo Suh, Chi Dae Kim, Jae Ho Kim, Morris J Birnbaum, Sun Sik Bae.   

Abstract

Akt plays pivotal roles in many physiological responses including growth, proliferation, survival, metabolism, and migration. In the current studies, we have evaluated the isoform-specific role of akt in lysophosphatidic acid (LPA)-induced cell migration. Ascites from ovarian cancer patients (AOCP) induced mouse embryo fibroblast (MEF) cell migration in a dose-dependent manner. On the other hand, ascites from liver cirrhosis patients (ALCP) did not induce MEF cell migration. AOCP-induced MEF cell migration was completely blocked by pre-treatment of cells with LPA receptor antagonist, Ki16425. Both LPA- and AOCP-induced MEF cell migration was completely attenuated by PI3K inhibitor, LY294002. Furthermore, cells lacking Akt1 displayed defect in LPA-induced cell migration. Re-expression of Akt1 in DKO (Akt1-/-Akt2-/-) cells restored LPA-induced cell migration, whereas re-expression of Akt2 in DKO cells could not restore the LPA-induced cell migration. Finally, Akt1 was selectively phosphorylated by LPA and AOCP stimulation. These results suggest that LPA is a major factor responsible for AOCP-induced cell migration and signaling specificity of Akt1 may dictate LPA-induced cell migration.

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Year:  2008        PMID： 18779657      PMCID： PMC2679274          DOI： 10.3858/emm.2008.40.4.445

Source DB:  PubMed          Journal:  Exp Mol Med        ISSN： 1226-3613            Impact factor:   8.718


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