Fig. 10

Schematic representation of SOCE activation in 32D-JAK2-V617F cells upon EPO stimulation. The JAK2-V617F mutation induces constitutive activation of the JAK2 kinases. Consequently, multiple tyrosine residues on the EPO receptor undergo phosphorylation. Moreover, JAK2 kinases then phosphorylate signal transducer and activator of transcription (STAT) molecules, facilitating their translocation to the nucleus, where they induce gene transcription. Concurrently, phospholipase C gamma-1 (PLCγ-1) is overactivated, which subsequently generates inositol trisphosphate (IP3). IP3 binds directly to its intracellular IP3 receptors (IP3R), resulting in the release of calcium from the endoplasmic reticulum (ER) stores into the cytosol. Subsequent replenishment of intracellular calcium stores occurs through store-operated calcium entry (SOCE) mediated by transmembrane proteins located on the ER and plasma membrane