Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions
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 comprehens...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2013.25 |
| _version_ | 1797280444098543616 |
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| author | Mathieu Courcelles Christophe Frémin Laure Voisin Sébastien Lemieux Sylvain Meloche Pierre Thibault |
| author_facet | Mathieu Courcelles Christophe Frémin Laure Voisin Sébastien Lemieux Sylvain Meloche Pierre Thibault |
| author_sort | Mathieu Courcelles |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:40:23Z |
| format | Article |
| id | doaj.art-63a9c0c7ea4a45a89d64dcbb76dbf6d0 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:40:23Z |
| publishDate | 2013-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-63a9c0c7ea4a45a89d64dcbb76dbf6d02024-03-03T08:20:01ZengSpringer NatureMolecular Systems Biology1744-42922013-01-0191n/an/a10.1038/msb.2013.25Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functionsMathieu Courcelles0Christophe Frémin1Laure Voisin2Sébastien Lemieux3Sylvain Meloche4Pierre Thibault5Institute for Research in Immunology and Cancer, Université de Montréal Montreal Quebec CanadaInstitute for Research in Immunology and Cancer, Université de Montréal Montreal Quebec CanadaInstitute for Research in Immunology and Cancer, Université de Montréal Montreal Quebec CanadaInstitute for Research in Immunology and Cancer, Université de Montréal Montreal Quebec CanadaInstitute for Research in Immunology and Cancer, Université de Montréal Montreal Quebec CanadaInstitute for Research in Immunology and Cancer, Université de Montréal Montreal Quebec CanadaThe 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.https://doi.org/10.1038/msb.2013.25bioinformaticscell signalingMAP kinasesphosphoproteomicsphosphorylation dynamics |
| spellingShingle | Mathieu Courcelles Christophe Frémin Laure Voisin Sébastien Lemieux Sylvain Meloche Pierre Thibault Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions Molecular Systems Biology bioinformatics cell signaling MAP kinases phosphoproteomics phosphorylation dynamics |
| title | Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions |
| title_full | Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions |
| title_fullStr | Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions |
| title_full_unstemmed | Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions |
| title_short | Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions |
| title_sort | phosphoproteome dynamics reveal novel erk1 2 map kinase substrates with broad spectrum of functions |
| topic | bioinformatics cell signaling MAP kinases phosphoproteomics phosphorylation dynamics |
| url | https://doi.org/10.1038/msb.2013.25 |
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