A. number of stimuli, including growth factors, cytokines, PAMPs, ROS, and environmental stresses activate the JNK signaling pathway through a 3-tier kinase cascade that includes MAP3Ks (ASK1, TAK1, MEKKs and MLKs), MAP2Ks (MKK4 and MKK7), and JNKs. Activated JNKs phosphorylate their substrates, which include transcription factors (c-Jun, JunB, JunD, p53, and c-Myc) and mitochondrial proteins (Bcl-2, Bid, Bim, Bax, and Mcl-1), to induce various biological responses.
B. The JNK protein contains a conserved dual phosphorylation Thr-Pro-Tyr motif in its activation loop and has a common substrate docking site in C-terminus and a glutamate/aspartate domain in its N-terminus to mediate interactions with MAP2Ks, phosphatases, and substrates.