Cell fate decisions are specified by the dynamic ERK interactome

von Kriegsheim, A. et al. (2009) Cell fate decisions are specified by the dynamic ERK interactome. Nature Cell Biology, 11(12), pp. 1458-1464. (doi: 10.1038/ncb1994)

Abstract

Extracellular signal-regulated kinase (ERK) controls fundamental cellular functions, including cell fate decisions(1,2). In PC12, cells shifting ERK activation from transient to sustained induces neuronal differentiation(3). As ERK associates with both regulators and effectors(4), we hypothesized that the mechanisms underlying the switch could be revealed by assessing the dynamic changes in ERK-interacting proteins that specifically occur under differentiation conditions. Using quantitative proteomics, we identified 284 ERK-interacting proteins. Upon induction of differentiation, 60 proteins changed their binding to ERK, including many proteins that were not known to participate in differentiation. We functionally characterized a subset, showing that they regulate the pathway at several levels and by different mechanisms, including signal duration, ERK localization, feedback, crosstalk with the Akt pathway and differential interaction and phosphorylation of transcription factors. Integrating these data with a mathematical model confirmed that ERK dynamics and differentiation are regulated by distributed control mechanisms rather than by a single master switch.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kolch, Prof Walter and Orton, Dr Richard and Morrice, Dr Nicholas
• Authors: von Kriegsheim, A., Baiocchi, D., Birtwistle, M., Sumpton, D., Bienvenut, W., Morrice, N., Yamada, K., Lamond, A., Kalna, G., Orton, R., Gilbert, D., and Kolch, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Nature Cell Biology
• ISSN: 1465-7392
• Published Online: 22 November 2009