Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects

Douglas A. Harrison, Richard Binari, Theresa Stines Nahreini, Michael Gilman, Norbert Perrimon

Research output: Contribution to journalArticlepeer-review

388 Scopus citations


In mammals, many cytokines and growth factors stimulate members of the Janus kinase (JAK) family to transduce signals for the proliferation and differentiation of various cell types, particularly in hematopoietic lineages. Mutations in the Drosophila hopscotch (hop) gene, which encodes a JAK, also cause proliferative defects, Loss-of-function alleles result in lethality and underproliferation of diploid tissues of the larva, A dominant gain-of-function allele, Tumorous-lethal (hop(Tum-l)), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs. We show that a single amino acid change in Hop is associated with the hop(Tum-l) mutation. Overexpression of either wild-type hop or hop(Tum-l) in the larval lymph glands causes melanotic tumors and lymph gland hypertrophy indistinguishable from the original hop(Tum-l) mutation. In addition, overexpression of Hop in other tissues of the larva leads to pattern defects in the adult or to lethality. Finally, overexpression of either hop or hop(Tum-l) in Drosophila cell culture results in tyrosine phosphorylation of Hop protein. However, overexpression of hop(Tum-l) results in greater phosphorylation than overexpression of the wild-type. We conclude that hop(Tum-l) encodes a hyperactive Hop kinase and that overactivity of Hop in lymph glands causes malignant neoplasia of Drosophila blood cells.

Original languageEnglish
Pages (from-to)2857-2865
Number of pages9
JournalEMBO Journal
Issue number12
StatePublished - 1995


  • Drosophilia
  • Hematopoiesis
  • JAK tyrosine kinase
  • Neoplasia
  • Signal transduction

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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