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JAK signaling in megakaryopoiesis. Cytokine binding to its cellular receptor leads to dimerization and phosphorylation that in turn binds and activates JAK, leading to downstream activation of RAS signaling and phosphorylation of STAT transcription factors. Receptors and kinases with activating mutations identified in AMKL include MPL, PDGFRB, JAK1, JAK2, JAK3, NRAS, and KRAS. Mutations in SH2B3 have been identified in DS-AMKL. SHC1, adapter molecule; SH2B3, inhibitor of JAK2.
