| Literature DB >> 19935650 |
Daniela Baiocchi1, Marc Birtwistle1, Alex von Kriegsheim1, David Sumpton1, Willy Bienvenut1, Nicholas Morrice2, Kayo Yamada3, Angus Lamond3, Gabriella Kalna1, Richard Orton4, David Gilbert5, Walter Kolch1,4.
Abstract
Extracellular signal-regulated kinase (ERK) controls fundamental cellular functions, including cell fate decisions. In PC12, cells shifting ERK activation from transient to sustained induces neuronal differentiation. As ERK associates with both regulators and effectors, 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.Entities:
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Year: 2009 PMID： 19935650 PMCID： PMC3839079 DOI： 10.1038/ncb1994
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824