Multisite phosphorylation of Erk5 in mitosis
[EN]The MAP kinase Erk5 plays important roles in cellular proliferation, and has recently been implicated in the regulation of mitosis. The classic pathway of Erk5 activation involves dual phosphorylation at its TEY microdomain by the upstream regulating kinase MEK5. Here we describe a second pathwa...
| Authors: | , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2010 |
| Country: | España |
| Institution: | Universidad de Salamanca (USAL) |
| Repository: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/167982 |
| Online Access: | http://hdl.handle.net/10366/167982 |
| Access Level: | Open access |
| Keyword: | Erk5 Mitosis Phosphorylation Amino Acid Motifs Protein Transport MAP Kinase Kinase 5 CDC2 Protein Kinase Mitogen-Activated Protein Kinase 7 Humans Cell Nucleus Cytosol Cell Line Amino Acid Sequence 2302 Bioquímica 2407 Biología Celular transporte de proteínas proteína cinasa CDC2 núcleo celular mitosis humanos secuencia de aminoácidos proteína cinasa activada por mitógenos 7 línea celular motivos de aminoácidos citosol MAP cinasa cinasa 5 fosforilación |
| Summary: | [EN]The MAP kinase Erk5 plays important roles in cellular proliferation, and has recently been implicated in the regulation of mitosis. The classic pathway of Erk5 activation involves dual phosphorylation at its TEY microdomain by the upstream regulating kinase MEK5. Here we describe a second pathway that controls Erk5 phosphorylation. This pathway is activated in mitotic cells and involves kinase activities distinct from MEK5. Studies aimed at identifying these kinases suggested that CDK1 activity is required to sustain Erk5 phosphorylation in mitosis, as treatment with RO3306, a CDK1 inhibitor, reversed mitotic phosphorylation of Erk5. Moreover, CDK1 co-precipitated with Erk5 in mitotic cells. The mitotic phosphorylation of Erk5 occurs at multiple sites located at its unique C-terminal region, within an Erk5 subdomain that has formerly been implicated in the control of the subcellular location of Erk5. Furthermore, molecular studies indicated that phosphorylation at these sites may participate in the control of the transit of Erk5 between the cytosol and the nucleus, in addition to regulating its transcriptional activity. Together, our results demonstrate the existence of a second Erk5 phosphorylation pathway, that is activated in mitosis, and that may participate in the regulation of Erk5 functions. |
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