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

377 Scopus citations

Abstract

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
Volume14
Issue number12
DOIs
StatePublished - 1995

Keywords

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

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)

Fingerprint

Dive into the research topics of 'Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects'. Together they form a unique fingerprint.

Cite this