Eicosanoid 12(S)-HETE activates phosphatidylinositol 3-kinase.
The arachidonic acid metabolite of 12 lipoxygenase, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) promotes metastatic behavior of tumor cells. In this study we set out to identify 12(S)-HETE signaling pathways, and their contribution to cellular functions in A431 epidermoid carcinoma. (1) 12(S)-HETE stimulated phosphotyrosine associated PI3 kinase activity. (2) 12(S)-HETE stimulated ERK1/2 in a PI3 kinase dependent manner. (3) PI3 kinase affected the 12(S)-HETE stimulated Raf/MEK/ERK cascade at the level of MEK. (4) 12(S)-HETE stimulated ERK1/2 via PKCzeta. (5) 12(S)-HETE stimulated cell migration on laminin, which was eliminated by PI3 kinase and cPKC inhibitors, but it was unaffected by inhibition of ERK1/2.
Szekeres
C K
CK
Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202, USA.
Trikha
M
M
Nie
D
D
Honn
K V
KV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D019869:Phosphatidylinositol 3-Kinases; C081975:protein kinase C eta; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases