The kinase domain of Drosophila Tribbles is required for turnover of fly C/EBP during cell migration

Dev Biol. 2013 Mar 1;375(1):33-44. doi: 10.1016/j.ydbio.2012.12.016. Epub 2013 Jan 7.

Abstract

Drosophila Tribbles (Trbl) encodes the founding member of the Trib family of kinase-like proteins that regulate cell migration, proliferation, growth and homeostasis. Trbl was identified in a misexpression screen in the ovary as an antagonist of border cell migration and acts in part by directing turnover of the C/EBP protein encoded by the gene slow border cells (slbo). The ability of mammalian Trib isoforms to promote C/EBP turnover during tissue differentiation indicates that this function is highly conserved. To better understand the role of Trbl in cell migration, we tested specific Trbl antisera, a trbl null allele and Trbl transgenes bearing site-directed mutations. Trbl is expressed at high levels in the nuclei of follicle cell epithelia and is downregulated in delaminating epithelia as expression of Slbo (C/EBP) is upregulated. This complementary pattern of expression during subsequent cell migration is achieved by negative feedback whereby slbo represses Trbl expression and trbl is necessary and sufficient to promote Slbo protein turnover. A series of point mutations that scan the conserved kinase domain of Trbl reveal that the conserved DLK catalytic loop is required for Trbl-Slbo binding and turnover, as well as for interactions between Trbl subunits, suggesting a mechanism of Trbl function.

Publication types

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

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Catalytic Domain
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation
  • Cell Movement* / genetics
  • Cell Proliferation
  • Drosophila / cytology*
  • Drosophila / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / immunology
  • Drosophila Proteins / metabolism*
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Mutation
  • Oogenesis / genetics
  • Ovary / cytology
  • Ovary / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / immunology
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Transgenes

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Cell Cycle Proteins
  • Drosophila Proteins
  • RNA, Small Interfering
  • trbl protein, Drosophila
  • slbo protein, Drosophila
  • Protein-Serine-Threonine Kinases