Fig. 6 | Signal Transduction and Targeted Therapy

Fig. 6

From: Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery

Fig. 6

MAP3K-MAP2K-MAPK signaling pathway. In a typical MAPK cascade, MAP3K activates MAP2K (also known as MKK, MEK) by phosphorylating two conserved Ser/Thr residues in the activation loop, and the MAP2Ks directly phosphorylate MAPKs. The activation of MAPK cascades is initiated by various extracellular stimuli, including growth factors, G-protein-coupled receptor (GPCR) signaling, stress, and cytokines. Activated Ras recruits and activates Raf, which phosphorylates and activates downstream MEK1/2. MEK1/2 then phosphorylates ERK1/2, which translocates to the nucleus and regulates gene transcription. Stress signals (e.g., reactive oxygen species or osmotic stress) and cytokines activate distinct MAPKKKs, leading to the phosphorylation of different MAPKKs. MKK4/7 phosphorylates and activates JNK/p38 MAPK, while MKK3/6 phosphorylates p38 MAPK. The hierarchical organization of the MAPK pathways ensures signal specificity, playing a critical role in cell apoptosis, cell survival, and other cellular events. This figure was created with BioRender.com

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