Control of TrkA-induced cell death by JNK activation and differential expression of TrkA upon DNA damage.
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.
Jung
Eun Joo
EJ
Department of Biochemistry and Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu 660-751, Korea.
Kim
Deok Ryong
DR
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*
D000873:Anthracenes; D020033:Protein Isoforms; C432165:pyrazolanthrone; D020917:Receptor, trkA; D048031:JNK Mitogen-Activated Protein Kinases; D002166:Camptothecin