TG1019/OXE, a Galpha(i/o)-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis.
We have previously identified a Galpha(i/o)-protein-coupled receptor (TG1019/OXE) using 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) as its ligand. We investigated signal transduction from TG1019 following stimulation with 5-oxo-ETE and role of TG1019 in 5-oxo-ETE-induced chemotaxis, using Chinese hamster ovary cells expressing TG1019 (CHO/TG1019 cells). 5-Oxo-ETE induced intracellular calcium mobilization and rapid activation of MEK/ERK and PI3K/Akt pathways in CHO/TG1019 cells. CHO/TG1019 cells stimulated with 5-oxo-ETE and other eicosanoids exhibited chemotaxis with efficacies related to agonistic activity of each eicosanoid for TG1019. Pretreatment of the cells with pertussis toxin, a phospholipase C (PLC) inhibitor (U73122) or a PI3K inhibitor (LY294002), markedly suppressed 5-oxo-ETE-induced chemotaxis, whereas pretreatment with a MEK inhibitor (PD98059) had no significant effect on the chemotaxis. Our results show that TG1019 mediates 5-oxo-ETE-induced chemotaxis and that signals from TG1019 are transduced via Galpha(i/o) protein to PLC/calcium mobilization, MEK/ERK, and PI3K/Akt, among which PLC and PI3K would play important roles in the chemotaxis.
Hosoi
Takeshi
T
Discovery Research Laboratories, Tanabe Seiyaku Co. Ltd., 2-50 Kawagishi-2-chome, Toda-shi, Saitama 335-8505, Japan.
Sugikawa
Emiko
E
Chikada
Aiko
A
Koguchi
Yutaka
Y
Ohnuki
Tetsuo
T
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage*; D016466:CHO Cells; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D001095:Arachidonic Acids; C504018:OXER1 protein, human; D018055:Receptors, Eicosanoid; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid