Mitogen-activated protein kinase 9 (MAPK9) isoform alpha-2 (JNK2α2)

Mitogen-activated protein kinase 9 (MAPK9) isoform alpha-2, commonly known as JNK2α2, is a member of the c-Jun N-terminal kinase (JNK) family that plays a pivotal role in the cellular response to environmental stress and inflammatory signals (UniProt P45984). It is one of several isoforms generated by the alternative splicing of the MAPK9 gene, specifically characterized by the inclusion of exon 6a and the longer C-terminal exon 10 (Gupta et al., 1996). JNK2α2 functions as a serine/threonine kinase that phosphorylates the N-terminal activation domain of the c-Jun transcription factor, thereby modulating the activity of the AP-1 transcription complex and regulating genes involved in cell proliferation and apoptosis (Bogoyevitch & Kobe, 2006). In many disease contexts, particularly oncology, JNK2α2 is implicated in promoting tumor cell survival and resistance to chemotherapy, making it a significant target for therapeutic intervention (Bubici & Papa, 2014). While most current pharmacological agents are pan-JNK inhibitors, such as Tanzisertib and SP600125, there is ongoing research into isoform-specific targeting to minimize the side effects associated with broad JNK inhibition (Koch et al., 2015).

Other names

c-Jun N-terminal kinase 2 alpha-2Stress-activated protein kinase 1aSAPK1aMAPK9 isoform 2JNK2-a2

ATP-competitive inhibition of the kinase domain, preventing the phosphorylation of downstream substrates such as c-Jun.