The JNK signalling pathway (adapted from http://www.sabiosciences.com/). Upstream events are poorly defined, but in the case of growth factors and the cytokine TNF are known to involve G proteins such as Rac and cdc-42 and the protein TRAF2. Activated JNK1 and JNK2 isoforms phosphorylate the AP-1 subunit c-Jun, increasing its transcriptional activity. ASK1, apoptosis signal-stimulating kinase 1; MLK, mixed-lineage protein kinases; TAK1, transforming growth factor-β-activated kinase-1.