Proteomic analysis of SP 600125‐controlled T rk A ‐dependent targets in SK ‐ N ‐ MC neuroblastoma cells: I nhibition of T rk A activity by SP 600125

The c‐ J un 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 ( T rk A ) neurotrophin receptor. In this study, we investigated JNK inhibitor SP 600125‐controlled T rk A ‐dependent targets by proteomic analysis to better understand an involvement of JNK in T rk A ‐mediated signaling pathways. PDQ uest image analysis and protein identification results showed that hn RNP C 1/ C 2, α‐tubulin, β‐tubulin homolog, actin homolog, and e IF ‐5A‐1 protein spots were upregulated by ectopic expression of T rk A , whereas α‐enolase, peroxiredoxin‐6, PROS ‐27, HSP 70, PP 1‐gamma, and PDH E 1‐alpha were downregulated by T rk A , and these T rk A ‐dependent upregulation and downregulation were significantly suppressed by SP 600125. Notably, T rk A largely affected certain PTM (s) but not total protein amounts of the SP 600125‐controlled T rk A ‐dependent targets. Moreover, SP 600125 strongly suppressed T rk A ‐mediated tyrosine phosphorylation signaling pathways as well as JNK signaling, indicating that SP 600125 could function as a T rk A inhibitor. Taken together, our results suggest that T rk A could play an important role in the cytoskeleton, cell death, cellular processing, and glucose metabolism through activation or inactivation of the SP 600125‐controlled T rk A ‐dependent targets.