title: Control of TrkA-induced cell death by JNK activation and differential expression of TrkA upon DNA damage.
abstract: TrkA, a receptor for nerve growth factor, plays a crucial role in neuronal cell growth and differentiation. However, overactivation of TrkA signaling leads to cell death in various cell types. TrkA-mediated cell death shows some similarities to DNA damage-induced cell death. In this study, we examined how TrkA-induced cell death is regulated upon DNA damage. Cytoplasmic expression of TrkA protein was differentially modulated during the camptothecin-induced DNA damage response in TrkA-expressing U2OS cells. TrkA-induced cell death was synergistically increased by DNA damage, but it was blocked in the presence of the JNK inhibitor SP600125. Overexpression of a 54-kDa JNK isoform (JNK1alpha2) aggravated TrkA-induced cell death and was associated with TrkA functional activation. These results suggest that TrkA shares a functional connection with other mediators in the DNA damage response via JNK signaling.
authors.affiliation: Department of Biochemistry and Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu 660-751, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Jung
authors.forename: Deok Ryong
authors.initials: DR
authors.lastname: Kim
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D020033:Protein Isoforms; C432165:pyrazolanthrone; D020917:Receptor, trkA; D048031:JNK Mitogen-Activated Protein Kinases; D002166:Camptothecin