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

Abstract

The c-Jun NH(2)-terminal kinase (JNK) signaling pathway participates in many physiological functions. In the current study we reported the cloning and characterization of five novel JNK2 transcript variants, which were designated as JNK2alpha3, JNK2alpha4, JNK2beta3, JNK2gamma1 and JNK2gamma2, respectively. Among them, JNK2alpha4 and JNK2gamma2 are potential non-coding RNA because they contain pre-mature stop codons. Both JNK2alpha3 and JNK2beta3 contain an intact kinase domain, and both encode a protein product of 46 kDa, the same as those of JNK2alpha1 and JNK2beta1. JNK2gamma1 contains a disrupted kinase domain and it showed a disable function. When over-expressed in mammalian cells, JNK2alpha3 showed higher activity on AP-1 than that of JNK2beta3 and JNK2gamma1. Furthermore, JNK2alpha3 and JNK2beta3 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.