An endogenous redox molecule, thioredoxin, regulates transactivation of epidermal growth factor receptor and activation of NF-kappaB by lysophosphatidic acid.
Lysophosphatidic acid (LPA) is the smallest and simplest of all the glycerophospholipids that activates a specific GTP-binding protein coupled receptor to evoke multiple cellular responses. In this paper, we have demonstrated that LPA stimulates nuclear factor (NF)-kappaB-dependent gene induction in a neuronal cell line, NG108-15 and that this is under redox regulation by an endogenous molecule, thioredoxin. We also have shown that redox-sensitive transactivation of epidermal growth factor receptor by LPA confers NF-kappaB activation and small GTPase proteins are involved in this pathway.
Hirota
K
K
Department of Anesthesia, Kyoto University Hospital, Kyoto University, Japan. khirota@kuhp.kyoto-u.ac.jp
Murata
M
M
Itoh
T
T
Yodoi
J
J
Fukuda
K
K
D000818:Animals; D002460:Cell Line; D004274:DNA, Recombinant; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004274:DNA, Recombinant; D008246:Lysophospholipids; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D013879:Thioredoxins; D008156:Luciferases; D066246:ErbB Receptors; D020962:Heterotrimeric GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins