Human tribbles, a protein family controlling mitogen-activated protein kinase cascades

  • J Biol Chem. 2004 Oct 8;279(41):42703-8. doi: 10.1074/jbc.M407732200.
Endre Kiss-Toth  1 ,  Stephanie M Bagstaff ,  Hye Y Sung ,  Veronika Jozsa ,  Clare Dempsey ,  Jim C Caunt ,  Kevin M Oxley ,  David H Wyllie ,  Timea Polgar ,  Mary Harte ,  Luke A J O'neill ,  Eva E Qwarnstrom ,  Steven K Dower
Affiliations
  • 1. Cardiovascular Research Unit, University of Sheffield, Northern General Hospital, Sheffield S5 7AU, United Kingdom. [email protected]
PMID: 15299019 DOI: 10.1074/jbc.M407732200
Abstract

Control of mitogen-activated protein kinase (MAPK) cascades is central to regulation of many cellular responses. We describe here human tribbles homologues (Htrbs) that control MAPK activity. MAPK kinases interact with Trbs and regulate their steady state levels. Further, Trbs selectively regulate the activation of extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38 MAPK with different relative levels of activity for the three classes of MAPK observed depending on the level of Trb expression. These results suggest that Trbs control both the extent and the specificity of MAPK kinase activation of MAPK.