This report describes fly models of JAK2-related myeloproliferative disorders or myeloproliferative neoplasias (MPNs); see the OMIM report for JAK2 (MIM:147796). The JAK2 gene encodes a non-receptor tyrosine kinase that plays a role in the JAK-STAT signaling pathway and is involved in regulation of many developmental processes. There is a single fly ortholog of JAK2, Dmel\hop, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Several other human genes, including JAK1, TYK2, and JAK3, are also orthologous to Dmel\hop.
The human JAK2 gene has not been introduced into flies. The pathogenic allele V617F, which exhibits constitutive tyrosine kinase activity, is responsible for the majority of identified JAK2-related myeloproliferative disorders.
Amorphic mutations of Dmel\hop, when homozygous, result in lethality at the larval or pupal stages; mutant animals exhibit segmentation defects. A well-characterized gain-of-function mutation is dominant; heterozygous animals exhibit additional cellular proliferation in the larval lymph glands, a massive increase in circulating haemocytes, and formation of melanotic tumors in both larvae and adults. Phenotypic assays using Dmel\hop mutations have allowed characterization of genetic interactions. Physical interactions of the hop protein have been described; see below and in the gene report for hop.
See the pathway report 'JAK-STAT Signaling Pathway' (FBgg0000883) for a listing of genes encoding core components and regulators of this pathway in flies.
[updated Jun. 2018 by FlyBase; FBrf0222196]
The JAK2 V617F allele has been found in most cases of polycythemia vera and half of the cases of essential thrombocythemia and primary myelofibrosis (Baxter et al., 2005; pubmed:15781101).
The pathogenic allele JAK2V617F, which exhibits constitutive tyrosine kinase activity, is responsible for the majority of JAK2-related myeloproliferative disorders. (Levine and Gilliland, 2007; pubmed:17133099).
Mutations in the Janus kinase 2 (JAK2) gene are implicated in multiple myeloproliferative disorders, including acute myeloid leukemia (MIM:601626), erythrocytosis (MIM:133100), thrombocythemia-3 (MIM:614521), polycythemia vera (MIM:263300), and myelofibrosis (MIM:254450).
The JAK2 gene encodes a non-receptor tyrosine kinase that plays a role in the JAK-STAT signaling pathway; it is involved in regulation of many developmental processes, including hematopoiesis. [From Gene Cards, JAK2; 2016.03.11]
JAK2 kinase is a member of a family of tyrosine kinases involved in cytokine receptor signaling. [from MIM:147796; 2016.03.10]
Many to one: 4 human to 1 Drosophila; the other orthologous human genes are JAK1, TYK2, and JAK3; additional lower scoring orthologs also exist in humans.
Moderate-scoring ortholog of human JAK1 and JAK2; low-to-moderate-scoring ortholog of human TYK2 and JAK3 (1 Drosophila to 4 human); additional lower scoring orthologs exist in humans. Dmel\hop shares 24% identity and 39-41% similarity with JAK1 and JAK2.
