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Molecular cloning and characterization of novel human JNK2 (MAPK9) transcript variants that show different stimulation activities on AP-1

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The c-Jun NH2-terminal kinase (JNK) signaling pathway participates in many physiological functions. In the current study we reported the cloning and characterization of five novel JNK2transcript variants, which were designated as JNK2α3, JNK2α4,JNK2β3, JNK2γ1 and JNK2γ2, respectively. Among them,JNK2α4 and JNK2γ2 are potential non-coding RNA because they contain pre-mature stop codons. Both JNK2α3 and JNK2β3contain an intact kinase domain, and both encode a protein product of 46 kDa, the same as those of JNK2α1 and JNK2β1. JNK2γ1 contains a disrupted kinase domain and it showed a disable function. When over-expressed in mammalian cells,JNK2α3 showed higher activity on AP-1 than that of JNK2β3and JNK2γ1. Furthermore, JNK2α3 and JNK2β3 showed different levels of substrate phosphorylation, although they both could promote the proliferation of 293T cells. Our results further demonstrate that JNK2 isoforms preferentially target different substrates and may regulate the expression of various target genes.

Abstract

The c-Jun NH2-terminal kinase (JNK) signaling pathway participates in many physiological functions. In the current study we reported the cloning and characterization of five novel JNK2transcript variants, which were designated as JNK2α3, JNK2α4,JNK2β3, JNK2γ1 and JNK2γ2, respectively. Among them,JNK2α4 and JNK2γ2 are potential non-coding RNA because they contain pre-mature stop codons. Both JNK2α3 and JNK2β3contain an intact kinase domain, and both encode a protein product of 46 kDa, the same as those of JNK2α1 and JNK2β1. JNK2γ1 contains a disrupted kinase domain and it showed a disable function. When over-expressed in mammalian cells,JNK2α3 showed higher activity on AP-1 than that of JNK2β3and JNK2γ1. Furthermore, JNK2α3 and JNK2β3 showed different levels of substrate phosphorylation, although they both could promote the proliferation of 293T cells. Our results further demonstrate that JNK2 isoforms preferentially target different substrates and may regulate the expression of various target genes.

참고문헌 (20)

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