Cytogenetic and molecular studies - Janus kinase 2 (JAK2) V617F
JAK2 and JAK-STAT signalling
- JAK2 - a non-receptor (cytoplasmic) tyrosine kinase
- Transduces signalling from receptors that have no intrinsic kinase activity: EPO receptor, thrombopoietin receptor (MPL), G-CSF receptor
- -> JAK-STAT pathway
- V617F = valine to phenylalanine at codon 617, exon 14, in the JH2 pseudokinase domain
- The pseudokinase domain normally autoinhibits the kinase domain
- -> loss of autoinhibition -> constitutive, cytokine-independent JAK-STAT signalling
- -> erythroid, megakaryocytic and granulocytic proliferation without EPO or TPO
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