Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics
Abstract The growth cone is essential for nerve growth and axon regeneration, which directly form and rearrange the neural network. Recently, to clarify the molecular signaling pathways in the growth cone that utilize protein phosphorylation, we performed a phosphoproteomics study of mammalian growt...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-019-0476-x |
| _version_ | 1818081561292046336 |
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| author | Michihiro Igarashi Shujiro Okuda |
| author_facet | Michihiro Igarashi Shujiro Okuda |
| author_sort | Michihiro Igarashi |
| collection | DOAJ |
| description | Abstract The growth cone is essential for nerve growth and axon regeneration, which directly form and rearrange the neural network. Recently, to clarify the molecular signaling pathways in the growth cone that utilize protein phosphorylation, we performed a phosphoproteomics study of mammalian growth cone membranes derived from the developing rodent brain and identified > 30,000 phosphopeptides from ~ 1200 proteins. We found that the phosphorylation sites were highly proline directed and primarily mitogen-activated protein kinase (MAPK) dependent, due to particular activation of c-jun N-terminal protein kinase (JNK), a member of the MAPK family. Because the MAPK/JNK pathway is also involved in axon regeneration of invertebrate model organisms such Caenorhabditis elegans and Drosophila, we performed evolutionary bioinformatics analysis of the mammalian growth cone phosphorylation sites. Although these sites were generally conserved within vertebrates, they were not necessarily conserved in these invertebrate model organisms. In particular, high-frequency phosphorylation sites (> 20 times) were less conserved than low-frequency sites. Taken together, the mammalian growth cones contain a large number of vertebrate-specific phosphorylation sites and stronger dependence upon MAPK/JNK than C. elegans or Drosophila. We conclude that axon growth/regeneration likely involves many vertebrate-specific phosphorylation sites. |
| first_indexed | 2024-12-10T19:08:10Z |
| format | Article |
| id | doaj.art-8fe9de2ee9f048829bf10ee546732c30 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-10T19:08:10Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-8fe9de2ee9f048829bf10ee546732c302022-12-22T01:36:50ZengBMCMolecular Brain1756-66062019-05-011211310.1186/s13041-019-0476-xEvolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomicsMichihiro Igarashi0Shujiro Okuda1Department of Neurochemistry and Molecular Cell Biology, Niigata University Graduate School of Medical and Dental SciencesLaboratory of Bioinformatics, Niigata University Graduate School of Medical and Dental SciencesAbstract The growth cone is essential for nerve growth and axon regeneration, which directly form and rearrange the neural network. Recently, to clarify the molecular signaling pathways in the growth cone that utilize protein phosphorylation, we performed a phosphoproteomics study of mammalian growth cone membranes derived from the developing rodent brain and identified > 30,000 phosphopeptides from ~ 1200 proteins. We found that the phosphorylation sites were highly proline directed and primarily mitogen-activated protein kinase (MAPK) dependent, due to particular activation of c-jun N-terminal protein kinase (JNK), a member of the MAPK family. Because the MAPK/JNK pathway is also involved in axon regeneration of invertebrate model organisms such Caenorhabditis elegans and Drosophila, we performed evolutionary bioinformatics analysis of the mammalian growth cone phosphorylation sites. Although these sites were generally conserved within vertebrates, they were not necessarily conserved in these invertebrate model organisms. In particular, high-frequency phosphorylation sites (> 20 times) were less conserved than low-frequency sites. Taken together, the mammalian growth cones contain a large number of vertebrate-specific phosphorylation sites and stronger dependence upon MAPK/JNK than C. elegans or Drosophila. We conclude that axon growth/regeneration likely involves many vertebrate-specific phosphorylation sites.http://link.springer.com/article/10.1186/s13041-019-0476-xGrowth conePhosphoproteomicsBioinformaticsMAPKEvolutionVertebrates |
| spellingShingle | Michihiro Igarashi Shujiro Okuda Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics Molecular Brain Growth cone Phosphoproteomics Bioinformatics MAPK Evolution Vertebrates |
| title | Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics |
| title_full | Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics |
| title_fullStr | Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics |
| title_full_unstemmed | Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics |
| title_short | Evolutionary analysis of proline-directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics |
| title_sort | evolutionary analysis of proline directed phosphorylation sites in the mammalian growth cone identified using phosphoproteomics |
| topic | Growth cone Phosphoproteomics Bioinformatics MAPK Evolution Vertebrates |
| url | http://link.springer.com/article/10.1186/s13041-019-0476-x |
| work_keys_str_mv | AT michihiroigarashi evolutionaryanalysisofprolinedirectedphosphorylationsitesinthemammaliangrowthconeidentifiedusingphosphoproteomics AT shujirookuda evolutionaryanalysisofprolinedirectedphosphorylationsitesinthemammaliangrowthconeidentifiedusingphosphoproteomics |