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| Subject Categories: Signal Transduction | Development |
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| The EMBO Journal
(2004) 23, 4770–4779, doi:10.1038/sj.emboj.7600467 Published online 11 November 2004 |
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| Scaffolding by ERK3 regulates MK5 in development |
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Stefanie Schumacher1, Kathrin Laa 1, Shashi Kant1, Yu Shi1, Axel Visel2, Achim D Gruber3, Alexey Kotlyarov1 and Matthias Gaestel1
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1 Medical School Hannover, Institute of Biochemistry, Hannover, Germany 2 Max Planck Institute of Experimental Endocrinology, Hannover, Germany 3 Department of Pathology, School of Veterinary Medicine Hannover, Hannover, Germany To whom correspondence should be addressed Matthias Gaestel, Medical School Hannover, Institute of Biochemistry, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Tel.: +49 511 532 2825; Fax: +49 511 532 2827; E-mail: gaestel.matthias@mh-hannover.de Received 19 July 2004; Accepted 11 October 2004; Published online 11 November 2004. |
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| Abstract |
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| Extracellular-regulated kinase 3 (ERK3, MAPK6) is an atypical member of the ERKs, lacking the threonine and tyrosine residues in the activation loop, carrying a unique C-terminal extension and being mainly regulated by its own protein stability and/or by autophosphorylation. Here we show that ERK3 specifically interacts with the MAPK-activated protein kinase 5 (MK5 or PRAK) in vitro and in vivo. Expression of ERK3 in mammalian cells leads to nuclear-cytoplasmic translocation and activation of MK5 and to phosphorylation of both ERK3 and MK5. Remarkably, activation of MK5 is independent of ERK3 enzymatic activity, but depends on its own catalytic activity as well as on a region in the C-terminal extension of ERK3. In mouse embryonic development, mRNA expression patterns of ERK3 and MK5 suggest spatiotemporal coexpression of both kinases. Deletion of MK5 leads to strong reduction of ERK3 protein levels and embryonic lethality at about stage E11, where ERK3 expression in wild-type mice is maximum, indicating a role of this signalling module in development. |
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| Keywords: MAP kinases, MAPKAP kinases, nucleocytoplasmic translocation, protein phosphorylation |
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