Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal transduction pathway in Drosophila

Dev Cell. 2003 Feb;4(2):179-90. doi: 10.1016/s1534-5807(03)00024-8.

Abstract

The JAK/STAT signal transduction pathway regulates many developmental processes in Drosophila. However, the functional mechanism of this pathway is poorly understood. In this report, we identify the Drosophila cyclin-dependent kinase 4 (Cdk4), which exhibits embryonic mutant phenotypes identical to those in the Hopscotch/JAK kinase and stat92E/STAT mutations. Specific genetic interactions between Cdk4 and hop mutations suggest that Cdk4 functions downstream of the HOP tyrosine kinase. We further show that Cyclin D-Cdk4 (as well as Cyclin E-Cdk2) binds and regulates STAT92E protein stability. STAT92E regulates gene expression for various biological processes, including the endocycle S phase. These data suggest that Cyclin D-Cdk4 and Cyclin E-Cdk2 play more versatile roles in Drosophila development.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning / genetics*
  • CDC2-CDC28 Kinases*
  • Cell Differentiation
  • Cell Polarity
  • Crosses, Genetic
  • Cyclin D
  • Cyclin E / genetics
  • Cyclin E / metabolism*
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Embryo, Nonmammalian / physiology*
  • Enzyme Activation
  • Eye / cytology
  • Eye / embryology
  • Female
  • Gene Expression Regulation, Developmental
  • Glycoproteins / metabolism
  • In Situ Hybridization
  • Insect Proteins / metabolism
  • Janus Kinase 1
  • Janus Kinases
  • Mutation
  • Oogenesis / physiology*
  • Ovarian Follicle / cytology
  • Ovarian Follicle / physiology*
  • Phenotype
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins*
  • STAT Transcription Factors
  • Signal Transduction*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors*

Substances

  • CycD protein, Drosophila
  • Cyclin D
  • Cyclin E
  • Cyclins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Glycoproteins
  • Insect Proteins
  • Proto-Oncogene Proteins
  • STAT Transcription Factors
  • Stat92E protein, Drosophila
  • Trans-Activators
  • Transcription Factors
  • upd1 protein, Drosophila
  • Protein-Tyrosine Kinases
  • Janus Kinase 1
  • Janus Kinases
  • hop protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cdk4 protein, Drosophila
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • cdk2 protein, Drosophila