Scaffolding by ERK3 regulates MK5 in development

Schumacher, Stefanie; Laaß, Kathrin; Kant, Shashi; Shi, Yu; Visel, Axel; Gruber, Achim D.; Kotlyarov, Alexey; Gaestel, Matthias

doi:10.1038/sj.emboj.7600467

Cited by 123 publications

(221 citation statements)

References 42 publications

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“…Human ERK3 interacts with MAPK-activated protein 5 (MK5 or PRAK) and spatio-temporal expression of ERK3 and MK5 suggest co-expression of both kinases [29]. In mice, deletion of mk5 leads to strong reduction of ERK3 protein levels and is lethal around E11, the time-point where expression levels of erk3 are maximal in wildtype mouse embryos [29,30]. This suggests an universal role of this MK5-ERK3 module in development.…”

Section: Erk3/4mentioning

confidence: 99%

Functions of the MAPK family in vertebrate‐development

2006

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The mitogen activated protein kinase (MAPK) family, consisting of the extracellular signal regulated protein kinase, c-Jun amino terminal MAPK and p38 subfamilies, is conserved in evolution throughout the plant and animal kingdoms. These proteins have been implicated in diverse cellular processes including cell growth, migration, proliferation, differentiation, survival and development. Gene-targeting approaches in mice, chickens, frogs and zebrafish revealed crucial roles of MAPK in vertebrate development. Gene-disruption or -silencing often lead to lethal effects, therefore the zebrafish ex utero development provides an excellent in vivo model to study the function of MAPK in early embryogenesis. In this review, we summarize the current understanding of the MAPK family function in vertebrate-development and place this into the perspective of possibilities for future research.

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Section: Erk3/4mentioning

confidence: 99%

Functions of the MAPK family in vertebrate‐development

2006

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“…No phosphorylation at Ser-15 was detected. Atypical MAP kinases ERK3 and ERK4 bind to and activate MK5 [67][68][69][70] and MK5 coimmunoprecipitates from murine heart lysates with ERK3, but not ERK4 or p38α [36]. Furthermore, MK5 may also be activated by PKA.…”

Section: Discussionmentioning

confidence: 99%

Characterization of hsp27 kinases activated by elevated aortic pressure in heart

et al. 2012

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Chronic hemodynamic overload results in left ventricular hypertrophy, fibroblast proliferation, and interstitial fibrosis. The small heat shock protein hsp27 has been shown to be cardioprotective and this requires a phosphorylatable form of this protein. To further understand the regulation of hsp27 in heart in response to stress, we investigated the ability of elevated aortic pressure to activate hsp27-kinase activities. Isolated hearts were subjected to retrograde perfusion and then snapfrozen. Hsp27-kinase activity was measured in vitro as hsp27 phosphorylation. Immune complex assays revealed that MK2 activity was low in non-perfused hearts and increased following crystalline perfusion at 60 or 120 mmHg. Hsp27-kinase activities were further studied following ion-exchange chromatography. Anion exchange chromatography on Mono Q revealed 2 peaks ('b' and 'c') of hsp27-kinase activity. A third peak 'a' was detected upon chromatography of the Mono Q flow-through fractions on the cation exchange resin, Mono S. The hsp27-kinase activity underlying peaks 'a' and 'c' increased as perfusion pressure was increased from 40 to 120 mmHg. In contrast, peak 'b' increased over pressures 60-100 mmHg but was decreased at 120 mmHg. Peaks 'a', 'b', and 'c' contained MK2 immunoreactivity, whereas MK3 and MK5 immunoreactivity was detected in peak 'a'. p38 MAPK and phospho-p38 MAPK were also detected in peaks 'b' and 'c' but absent from peak 'a'. Hsp27-kinase activity in peaks 'b' and 'c' (120 mmHg) eluted from a Superose 12 gel filtration column with an apparent molecular mass of 50-kDa. Hence, peaks 'b' and 'c' were not a result of MK2 forming complexes. In-gel hsp27-kinase assays revealed a single 49-kDa renaturable hsp27-kinase activity in peaks 'b' and 'c' at 60 mmHg, whereas several hsp27-kinases (p43, p49, p54, p66) were detected in peaks 'b' and 'c' from hearts perfused at 120 mmHg. Thus, multiple hsp27-kinases were activated in response to elevated aortic pressure in isolated, perfused rat hearts and hence may be implicated in regulating the cardioprotective effects of hsp27 and thus may represent targets for cardioprotective therapy.

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“…ERK3, constitutively expressed in orofacial tissue during GDs 12-14 (Turgeon et al, 2000), has been linked to MAPK-activated protein kinase-5 (MK5), identifying MK5 as a downstream target of ERK3 (Schumacher et al, 2004). Expression of ERK5 and MEK5, the upstream kinase of ERK5, was transiently increased from GD 12 to GD 14, suggesting their involvement in orofacial growth and/or differentiation.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiles of mitogen activated protein kinase signaling pathways in orofacial development

Singh

Yin

Pisano

et al. 2006

Birth Defects Research

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BACKGROUND: Formation of the mammalian orofacial region involves multiple signaling pathways regulating sequential expression of and interaction between molecular signals during embryogenesis. The present study examined the expression patterns of members of the MAPK family in developing murine orofacial tissue. METHODS: Total RNA was extracted from developing embryonic orofacial tissue during gestational days (GDs) 12-14 and used to prepare biotinylated cDNA probes, which were then denatured and hybridized to murine MAPK signaling pathways gene arrays. RESULTS: Expression of a number of genes involved in the (ERK1/2) cascade transiently increased in the embryonic orofacial tissue over the developmental period examined. Numerous members of the SAPK/JNK cascade were constitutively expressed in the tissue. Genes known to play a role in p38 MAPK signaling exhibited constitutive expression during orofacial development. Western blot analysis demonstrated that ERK2/1, p38, and SAPK/JNK kinases are present in embryonic orofacial tissue on each of GD 12, 13, and 14. By using phospho-specific antibodies, active ERK was shown to be temporally regulated during orofacial development. Minimal amounts of active p38 and active SAPK/JNK were detected in orofacial tissue during GDs 12-14. CONCLUSIONS: Our study documents specific expression patterns of genes coding for proteins belonging to the ERK1/2, p38, and SAPK/ JNK MAPK families in embryonic orofacial tissue. We also demonstrate that active, phosphorylated forms of ERK1/2 only were detected in the embryonic tissue investigated, suggesting a more central role for members of this family in embryonic orofacial development.

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Scaffolding by ERK3 regulates MK5 in development

Cited by 123 publications

References 42 publications

Functions of the MAPK family in vertebrate‐development

Functions of the MAPK family in vertebrate‐development

Characterization of hsp27 kinases activated by elevated aortic pressure in heart

Molecular profiles of mitogen activated protein kinase signaling pathways in orofacial development

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