Autotaxin promotes motility via G protein-coupled phosphoinositide 3-kinase γ in human melanoma cells

被引:31
作者
Lee, HY
Bae, GU
Jung, ID
Lee, JS
Kim, YK
Noh, SH
Stracke, ML
Park, CG
Lee, HW
Han, JW [1 ]
机构
[1] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea
[2] Konyang Univ, Coll Med, Nonsan 320711, South Korea
[3] Yonsei Univ, Coll Med, Canc Metastasis Res Ctr, Seoul 120752, South Korea
[4] Natl Canc Inst, NIH, Pathol Lab, Bethesda, MD 20892 USA
关键词
autotaxin; phosphoinositide; 3-kinase; p110; gamma; tumor cell motility;
D O I
10.1016/S0014-5793(02)02457-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autotaxin (ATX), an exo-nucleotide pyrophosphatase and phosphodiesterase, stimulates tumor cell motility at subnanomolar levels and augments invasiveness and angiogenesis. We investigated the role of G protein-coupled phosphoinositide 3-kinase gamma (PI3Kgamma) in ATX-mediated tumor cell motility stimulation. Pretreatment of human melanoma cell line A2058 with wortmannin or LY294002 inhibited ATX-induced motility. ATX increased the PI3K activity in p110gamma, but not p85, immunoprecipitates. This effect was abrogated by PI3K inhibitors or inhibited by pertussis toxin. Furthermore, stimulation of tumor cell motility by ATX was inhibited by catalytically inactive form of PI3Kgamma, strongly indicating the crucial role of PI3Kgamma for ATX-mediated motility in human melanoma cells. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:137 / 140
页数:4
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