RT Journal Article
T1 Competition between members of the tribbles pseudokinase protein family shapes their interactions with mitogen activated protein kinase pathways
A1 Guan, Hongtao
A1 Shuaib, Aban
A1 Davila de Leon, David
A1 Angyal, Adrienn
A1 Salazar Roa, María
A1 Velasco Díez, Guillermo
A1 Holcombe, Mike
A1 Dower, Steven
A1 Kiss-Toth, Endre
AB Spatio-temporal regulation of intracellular signalling networks is key to normal cellular physiology; dysregulation of which leads to disease. The family of three mammalian tribbles proteins has emerged as an important controller of signalling via regulating the activity of mitogen activated protein kinases (MAPK), the PI3-kinase induced signalling network and E3 ubiquitin ligases. However, the importance of potential redundancy in the action of tribbles and how the differences in affinities for the various binding partners may influence signalling control is currently unclear. We report that tribbles proteins can bind to an overlapping set of MAPK-kinases (MAPKK) in live cells and dictate the localisation of the complexes. Binding studies in transfected cells reveal common regulatory mechanisms and suggest that tribbles and MAPKs may interact with MAPKKs in a competitive manner. Computational modelling of the impact of tribbles on MAPK activation suggests a high sensitivity of this system to changes in tribbles levels, highlighting that these proteins are ideally placed to control the dynamics and balance of activation of concurrent signalling pathways.
PB Nature Porfolio
SN 2045-2322
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/97804
UL https://hdl.handle.net/20.500.14352/97804
LA eng
NO Guan, H., Shuaib, A., Leon, D. et al. Competition between members of the tribbles pseudokinase protein family shapes their interactions with mitogen activated protein kinase pathways. Sci Rep 6, 32667 (2016). https://doi.org/10.1038/srep32667
NO British Heart Foundation
NO European Commission
NO Instituto de Salud Carlos III
NO Biotechnology and Biological Sciences Research Council (UK)
NO Fondation Leducq (France)
DS Docta Complutense
RD 17 abr 2025