An amino acid substitution in the Drosophila hopTum-l Jak kinase causes leukemia-like hematopoietic defects

EMBO J. 1995 Apr 3;14(7):1412-20.

Abstract

Proteins of the Jak family of non-receptor kinases play important roles in mammalian hematopoietic signal transduction. They mediate the cellular response to a wide range of cytokines and growth factors. A dominant mutation in a Drosophila Jak kinase, hopscotchTumorous-lethal (hopTum-l), causes hematopoietic defects. Here we conduct a molecular analysis of hopTum-l. We demonstrate that the hopTum-l hematopoietic phenotype is caused by a single amino acid substitution of glycine to glutamic acid at residue 341. We generate a true revertant of the hopTum-l mutation, in which both the molecular lesion and the mutant hematopoietic phenotype revert back to wild type. We also examine the effects of the G341E substitution in transgenic flies. The results indicate that a mutant Jak kinase can cause leukemia-like abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Crosses, Genetic
  • DNA Primers
  • Drosophila Proteins
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Female
  • Genes, Lethal
  • Genotype
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology*
  • Heterozygote
  • Janus Kinases
  • Larva
  • Leukemia, Experimental
  • Male
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Point Mutation*
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Pupa
  • Transcription Factors

Substances

  • DNA Primers
  • Drosophila Proteins
  • Transcription Factors
  • Protein-Tyrosine Kinases
  • Janus Kinases
  • hop protein, Drosophila