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Fig. 1 | Journal of Hematology & Oncology

Fig. 1

From: The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy

Fig. 1

Target hyperactive Ras/RAF/MEK/ERK (MAPK) signaling for cancer therapy. The Ras/RAF/MEK/ERK (MAPK) signaling functions downstream of receptor tyrosine kinases (RTKs). Upon engagement by their ligands, RTKs activates guanine exchange factors, Sos proteins, which load GTP to Ras GTPases. Then, GTP-bound Ras GTPases recruit RAF/MEK heterodimers in cytosol to plasma membrane where they form transient tetramers through the side-to-side dimerization of RAFs. The RAF dimerization not only turns on RAFs but also loosens RAF/MEK heterodimerization and facilitates MEK homodimerization on RAF dimer surface, which leads to the activation of MEKs by RAFs. Once MEKs are activated, they phosphorylate ERKs, and then active ERKs phosphorylate a number of downstream effectors. In cancer cells, hyperactive Ras/RAF/MEK/ERK (MAPK) signaling arising from genetic mutations of Ras GTPases and BRAF can be targeted by small molecular inhibitors of Ras G12C, BRAF(V600E), MEK, and ERK

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