JAK2

Janus kinase 2

Ensembl:
ENSG00000096968
UniProt:
O60674
OMIM:
147796
Synonyms:
JTK10

Cilia effects upon perturbation of JAK2

Loss-of-function effect:
Longer cilia

Ciliogenesis screen results (4 screens)

  • Kim2016: No effect
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.13) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Human ciliopathy phenotype:
primary myelofibrosis; Myelofibrosis; myelofibrosis

Subcellular localization

basal body, cilia

Functional category

  • Ciliary assembly/disassembly; Non-motile cilium / primary cilium

Function

JAK2 localizes predominantly to the daughter centriole of the primary cilium in 3T3‐F442A fibroblasts and regulates cilia length and orientation as well as directional cell migration. Growth hormone (GH) stimulates relocation of growth hormone receptor to the cilium and shortens cilia, whereas pharmacological JAK2 inhibition or CRISPR‐mediated JAK2 knockout (KO) results in cilia elongation. Using a nocodazole washout assay, we find that JAK2 activity is required for proper control of cilia length during cilia re‐assembly. Centrosomal localization of JAK2 depends on both its SH2 domain and kinase activity, and JAK2 clones deficient in centrosomal targeting or kinase function demonstrate impaired control of cilia length and reduced cell proliferation compared with parental and JAK2 WT cells(PMID: 41676961).

Model organism evidence

Mus musculus (1 reference)

The severity of cilia-related syndromes (ciliopathies) ranges from viable with fertility defects to embryonic lethal, often with different mutations in the same gene resulting in highly variable phenotypes.

PMIDs: 41352382