期刊
MOLECULAR SYSTEMS BIOLOGY
卷 9, 期 -, 页码 -出版社
WILEY
DOI: 10.1038/msb.2013.25
关键词
bioinformatics; cell signaling; MAP kinases; phosphoproteomics; phosphorylation dynamics
资金
- Canadian Institutes for Health Research (CIHR)
- BiT program
- Fonds de recherche sur la nature et les technologies du Quebec (FQRNT)
- Cole foundation
- French Association pour la Recherche contre le Cancer (ARC)
- Fonds de la recherche en sante du Quebec (FRSQ)
- National Science and Engineering Research Council (NSERC)
- CIHR
- Cancer Research Society
- Canadian Center of Excellence in Commercialization and Research
- Canada Foundation for Innovation
- FRSQ
The ERK1/2 MAP kinase pathway is an evolutionarily conserved signaling module that controls many fundamental physiological processes. Deregulated activity of ERK1/2 MAP kinases is associated with developmental syndromes and several human diseases. Despite the importance of this pathway, a comprehensive picture of the natural substrate repertoire and biochemical mechanisms regulated by ERK1/2 is still lacking. In this study, we used large-scale quantitative phosphoproteomics and bioinformatics analyses to identify novel candidate ERK1/2 substrates based on their phosphorylation signature and kinetic profiles in epithelial cells. We identified a total of 7936 phosphorylation sites within 1861 proteins, of which 155 classify as candidate ERK1/2 substrates, including 128 new targets. Candidate ERK1/2 substrates are involved in diverse cellular processes including transcriptional regulation, chromatin remodeling, RNA splicing, cytoskeleton dynamics, cellular junctions and cell signaling. Detailed characterization of one newly identified substrate, the transcriptional regulator JunB, revealed that ERK1/2 phosphorylate JunB on a serine adjacent to the DNA-binding domain, resulting in increased DNA-binding affinity and transcriptional activity. Our study expands the spectrum of cellular functions controlled by ERK1/2 kinases.
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