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

FEBS Letters

Lee, Jang-Soon¹  Han, Jeung-Whan³  Stracke, Mary L²  Kim, Yong Kee³  Park, Chang Gyo¹  Bae, Gyu-Un³  Jung, In Duk¹  Lee, Hyang Woo³  Noh, Sung Hoon⁴  Lee, Hoi Young¹ 

[1] College of Medicine, Konyang University, Nonsan 320-711, South Korea;Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA;College of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea;Cancer Metastasis Research Center, College of Medicine, Yonsei University, Seoul 120-752, South Korea

关键词: Autotaxin;    Phosphoinositide 3-kinase;    p110γ;    Tumor cell motility;    ATX;    autotaxin;    PDE;    phosphodiesterase;    PI3K;    phosphoinositide 3-kinase;    PtdIns;    phosphatidylinositols;    PtdIn(3)P;    phosphatidylinositol 3-phosphate;    NPP;    nucleotide-pyrophosphatase phosphodiesterase;    PTx;    pertussis toxin;   

DOI  :  10.1016/S0014-5793(02)02457-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Autotaxin (ATX), an exo-nucleotide pyrophosphatase and phosphodiesterase, stimulates tumor cell motility at sub-nanomolar levels and augments invasiveness and angiogenesis. We investigated the role of G protein-coupled phosphoinositide 3-kinase γ (PI3Kγ) 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 p110γ, 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 PI3Kγ, strongly indicating the crucial role of PI3Kγ for ATX-mediated motility in human melanoma cells

【 授权许可】

Unknown