Lysophosphatidic acid induces cell migration through the selective activation of Akt1

被引：0
作者：
Eun Kyoung Kim
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
机构：
[1] MRC for Ischemic Tissue Regeneration and Medical Research Institute,Department of Internal Medicine
[2] Korea.,Department of Obstetrics and Gynecology
[3] School of Medicine,undefined
[4] Pusan National University,undefined
[5] Busan 602-739,undefined
[6] Korea.,undefined
[7] School of Medicine,undefined
[8] Pusan National University,undefined
[9] Busan 602-739,undefined
[10] Korea.,undefined
[11] University of Pennsylvania,undefined
[12] School of Medicine,undefined
[13] Philadelphia,undefined
[14] Pennsylvania 19104,undefined
[15] USA.,undefined
来源：
Experimental & Molecular Medicine | 2008年 / 40卷
关键词：
ascites; cell movement; fibroblasts; lysophosphatidic acid; 1-phosphatidylinositol 3-kinase; proto-oncogen proteins c-akt;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
页码：445 / 452
页数：7
相关论文
共 228 条
  • [1] Ackah E(2005)Akt1/protein kinase Bα is critical for ischemic and VEGF-mediated angiogenesis J Clin Invest 115 2119-2127
  • [2] Yu J(2003)Isoform-specific regulation of insulin-dependent glucose uptake by Akt/ protein kinase B J Biol Chem 278 49530-49536
  • [3] Zoellner S(2006)PKBα is required for adipose differentiation of mouse embryonic fibroblasts J Cell Sci 119 889-897
  • [4] Iwakiri Y(2004)Lysophosphatidic Acid Stimulates Ovarian Cancer Cell Migration via a Ras-MEK Kinase 1 Pathway Cancer Res 64 4209-4217
  • [5] Skurk C(2001)Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ) Science 292 1728-1731
  • [6] Shibata R(2001)Akt1/PKBα is required for normal growth but dispensable for maintenance of glucose homeostasis in mice J Biol Chem 276 38349-38352
  • [7] Ouchi N(2000)Lysophosphatidic acid receptors Mol Pharmacol 58 1188-1196
  • [8] Easton RM(2002)Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2) Mol Cell Biol 22 6921-6929
  • [9] Galasso G(1999)Cellular survival: a play in three Akts Genes Dev 13 2905-2927
  • [10] Birnbaum MJ(2003)A role for cytoplasmic dynein and LIS1 in directed cell movement J Cell Biol 163 1205-1211
12345678910