情報生物学的手法による新規JNK結合分子の網羅的探索

概要

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The MAP kinase JNK is a key regulator of diverse cell signaling pathways, including stress response, cell growth, migration, differentiation and apoptosis. Recent studies have indicated that JNK targets both nuclear and extra-nuclear targets in vivo. However, the extra-nuclear targets of JNK are not fully understood. In this study, we detected JNK binding candidates by searching exhaustively for novel extra-nuclear proteins containing a JNK binding domain sequence motif in a protein sequence library. Among the candidates, binding affinities of Past-A, BMPRII and hypothetical protein DKFZp761017121 to JNK were investigated. The results showed that expressed Past-A(TM6-7) and BMPRII-CT, but not DKFZp761O17121 were associated with JNK in a pull-down assay in C0S7 cells. Moreover, we found that Past-A(TM6-7) and BMPRII-CT exhibited a higher affinity to JNK than to MAP kinase p38. The affinity of short-form BMPRII (BMPRII-SH), a splicing variant that lacks cytoplasmic tail region including JNK binding domain, to JNK was much lower than that of BMPRII. These results indicate that in silico investigations of JNK binding proteins using the JNK binding domain peptide sequence is a useful strategy to reveal novel extra-nuclear targets of JNK.原著
東北大学の論文