title: Proteomic analysis of SP600125-controlled TrkA-dependent targets in SK-N-MC neuroblastoma cells: inhibition of TrkA activity by SP600125.
abstract: The c-Jun N-terminal kinase (JNK) is well known to play an important role in cell death signaling of the p75 neurotrophin receptor. However, little has been studied about a role of JNK in the signaling pathways of the tropomyosin-related kinase A (TrkA) neurotrophin receptor. In this study, we investigated JNK inhibitor SP600125-controlled TrkA-dependent targets by proteomic analysis to better understand an involvement of JNK in TrkA-mediated signaling pathways. PDQuest image analysis and protein identification results showed that hnRNP C1/C2, α-tubulin, β-tubulin homolog, actin homolog, and eIF-5A-1 protein spots were upregulated by ectopic expression of TrkA, whereas α-enolase, peroxiredoxin-6, PROS-27, HSP70, PP1-gamma, and PDH E1-alpha were downregulated by TrkA, and these TrkA-dependent upregulation and downregulation were significantly suppressed by SP600125. Notably, TrkA largely affected certain PTM(s) but not total protein amounts of the SP600125-controlled TrkA-dependent targets. Moreover, SP600125 strongly suppressed TrkA-mediated tyrosine phosphorylation signaling pathways as well as JNK signaling, indicating that SP600125 could function as a TrkA inhibitor. Taken together, our results suggest that TrkA could play an important role in the cytoskeleton, cell death, cellular processing, and glucose metabolism through activation or inactivation of the SP600125-controlled TrkA-dependent targets.
authors.affiliation: Department of Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, South Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Jung
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Park
authors.forename: Ky Hyun
authors.initials: KH
authors.lastname: Chung
authors.forename: Choong Won
authors.initials: CW
authors.lastname: Kim
mesh_terms: D000873:Anthracenes / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D020917:Receptor, trkA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000873:Anthracenes; D020543:Proteome; C432165:pyrazolanthrone; D020917:Receptor, trkA; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Cell biology; JNK; PTM; Proteomic analysis; SP600125-controlled; TrkA-dependent targets