Expression of MUK/DLK/ZPK, an activator of the JNK pathway, in the nervous systems of the developing mouse embryo
Section snippets
Results and discussion
Originally identified as a subgroup of MAP kinases that are activated by cellular stress, and which regulate cell differentiation and apoptosis (Kyriakis and Avruch, 2001), JNK is now recognized as a key component of the signal transduction pathways involved in the regulation of planner cell polarity and cell migration, both of which are essential for ontogeny (Hirai et al., 2002, Weston and Davis, 2002, Xia and Karin, 2004). The multiplicity of cellular events regulated by JNK indicates that
Experimental procedures
Mouse embryos at embryonic day 10–16 were fixed overnight in 4% PFA at 4 °C and then embedded in paraffin wax. Paraffin sections (6 μm thick) were hydrolyzed, heated at 120 °C for 20 min in 10 mM sodium citrate, pH 6.0 and then immunohistochemically stained using a standard protocol. Briefly, sections were sequentially incubated with primary affinity-purified anti-MUK rabbit antibody raised against the C-terminal part of MUK (Hirai et al., 2002), anti-MAP2 monoclonal antibody (Sigma), rabbit
Acknowledgements
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Deciphering the multifunctional role of dual leucine zipper kinase (DLK) and its therapeutic potential in disease
2023, European Journal of Medicinal ChemistryAxon injury signaling and compartmentalized injury response in glaucoma
2019, Progress in Retinal and Eye ResearchCitation Excerpt :MKK4 and MKK7 have yet to be tested independently or together in a model of ocular hypertension. Upstream of JNK and the MAP2Ks are the MAP3Ks, most notably the dual leucine zipper kinase (DLK) and leucine-zipper bearing kinase (LZK), that are expressed in axons and contribute to axonal and somal degeneration after glaucomatous related injuries (Farley and Watkins, 2018; Fernandes et al., 2014; Gerdts et al., 2016; Hirai et al., 2005; Tedeschi and Bradke, 2013; Valakh et al., 2015; Watkins et al., 2013; Welsbie et al., 2013, 2017). The MAP3Ks often control the activation of different physiological and pathological pools of JNK (Chen et al., 2002; Craig et al., 2008).
Distinct functions of the dual leucine zipper kinase depending on its subcellular localization
2016, Cellular SignallingCitation Excerpt :Both, TNFα and IL-1β stimulate MLK3 kinase activity at least in part dependent on the activation of Rac/Cdc42 and the interaction with the Rac/Cdc42 interaction site (CRIB) within MLK3 [10–12]. DLK is expressed in many and diverse tissues like brain and the peripheral nervous system, β-cells and primary islets [8,13,14]. Mice lacking DLK die perinatally, exhibiting impaired axon growth and neuronal radial migration, absence of the anterior commissure and reduced apoptosis in multiple neuronal populations during development [15–17].
Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation
2015, Cell Host and MicrobeCitation Excerpt :Viral reactivation could be completed when these signaling pathways reach full threshold. As DLK and JIP-3 are expressed almost exclusively in neurons (Hirai et al., 2005; Kelkar et al., 2000), targeting them would be an effective mechanism to prevent HSV reactivation in response to multiple triggers. We have further defined phase I of reactivation as being dependent upon JNK signaling but independent of histone demethylase activity.
DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury
2014, Neurobiology of DiseaseCitation Excerpt :Five days after axonal injury pJNK fills RGC somas in wildtype retinas, but was not present in RGCs of Dlk−/− mice (Fig. 3A). These data were surprising since DLK is known to be expressed in axons and regulate axonal injury signaling (Eto et al., 2010; Hirai et al., 2005; Xiong et al., 2010). However, it is possible that there is some level of pJNK activation that is controlled by DLK in the proximal axon that was not observed by immunohistochemistry.