Mixed-lineage kinase control of JNK and p38 MAPK pathways

Gallo, Kathleen A.; Johnson, Gary L.

doi:10.1038/nrm906

Cited by 537 publications

(615 citation statements)

References 108 publications

Supporting

Mentioning

589

Contrasting

Unclassified

Order By: Relevance

“…For example, a gene regulated by EE in the striatum was MAP3K12 (also known as DLK, MUK, Zpk). MAP3K12 belongs to the MAP kinase-kinase-kinase (MAPKKK) class of protein kinases and regulates MAP kinases c-Jun amino-terminal kinase (JNK) via MAPKK7, which belongs to the MAP kinase-kinase class of protein kinases (Gallo and Johnson, 2002). MAP3K appears to be involved in neurodevelopment in mice (Hirai et al, 2005) as well as axon growth and neuronal migration (Hirai et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

et al. 2008

View full text Add to dashboard Cite

We have previously shown that environmental enrichment decreases the activating and rewarding effects of the psych psychostimulant cocaine and increases resistance to the neurotoxic effect of the Parkinson-inducing drug MPTP. These effects were accompanied by an increase in the striatal expression of the neurotrophin BDNF, an increase in the striatal levels of delta-Fos B and by a decrease in striatal levels of the dopamine transporter, the main molecular target for cocaine and MPTP. Here, we used cDNA arrays to investigate the effects of rearing mice in enriched environments from weaning to adulthood on the profile of expression of genes in the striatum focusing on genes involved in intracellular signalling and functioning. We found that mice reared in an enriched environment show several alterations in the levels of mRNA coding for proteins involved in cell proliferation, cell differentiation, signal transduction, transcription and translation, cell structure and meta metabolism. Several of these findings were further confirmed by real-time quantitative PCR and, in the case of protein kinase C lambda, also by western blot. These findings are the first description of alterations in striatal gene expression by an enriched environment. The striatal gene expression regulation by environment that we report here may play a role in the resistance to the effects of drugs of abuse and dopaminergic neurotoxins previously reported.

show abstract

Section: Discussionmentioning

confidence: 99%

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

et al. 2008

View full text Add to dashboard Cite

show abstract

“…DLK is a serine/threonine kinase and belongs to the mixed-lineage kinases that function as MAPKKK [18,32]. As such, DLK phosphorylates and activates the dualspecificity MAPKK MKK7 and MKK4, which in turn phosphorylate and activate the MAPK JNK [26,33,34].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of membrane depolarisation-induced transcriptional activity of cyclic AMP response element binding protein (CREB) by the dual-leucine-zipper-bearing kinase in a pancreatic islet beta cell line

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: The activation of the transcription factor cyclic AMP response element binding protein (CREB) by protein kinase A is inhibited by the human orthologue of the mitogen-activated protein kinase, dualleucine-zipper-bearing kinase (DLK) in teratocarcinoma cells. However, pancreatic beta cells are electrically excitable and a major pathway regulating CREB in these cells is membrane depolarisation, leading to calcium influx and activation of the calcium/calmodulin-dependent protein phosphatase calcineurin. Therefore, the effect of DLK on CREB activity induced by membrane depolarisation was investigated in the beta cell line HIT. Materials and methods: Reporter gene assays and biochemical techniques were used. Results: RT-PCR, Western blot analysis and immunohistochemistry demonstrated the expression of DLK in HIT cells and primary mouse islets. In transient transfection experiments, DLK inhibited both GAL4-CREB activity induced by membrane depolarisation, and transcription directed by the CREB binding site, the cyclic AMP response element. Furthermore, DLK inhibited the transcriptional activity conferred by the CREB coactivator, CREB binding protein, both under basal conditions and after membrane depolarisation. DLK was also effective in response to glucose, the most potent physiological stimulus and known to cause membrane depolarisation of beta cells. Inhibition of calcineurin enhanced DLK activity, whereas overexpression of calcineurin reduced the inhibition by DLK of transcription directed by cyclic AMP response element after membrane depolarisation. Conclusions/interpretation: These results demonstrate a calcineurin-sensitive inhibition by DLK of CREB activity after membrane depolarisation in pancreatic islet beta cells. This inhibition may, at least partially, be mediated at the coactivator level. The results thus suggest that DLK plays a role in the regulation of beta cell function, including insulin gene transcription and beta cell apoptosis.

show abstract

“…RhoA activates JNK in human culture cells in a G ␣12 -and G i -dependent (Nagao et al, 1999;Yamauchi et al, 2000) or Pak-independent manner (Teramoto et al, 1996), and Rac1 and Cdc42 mediate the activation of JNK by several stimuli (Davis, 2000; Gallo Johnson, 2002). Recently, it has been known that the Wnt/PCP pathway is an important signal cascade for JNK activation (Veeman et al, 2003b).…”

Section: Rhoa Is Required For the Activation Of Jnk By Wnt/ Pcp Pathwmentioning

confidence: 99%

“…Rac1 modulates JNK activation by means of the serine/threonine kinase, p65 PAK in mammalian cells (Zhang et al, 1995) and by MLK3 (Gallo and Johnson, 2002). In addition, Slpr, the Drosophila MLK, acts downstream of dRac1 in the Drosophila JNK pathway to produce dorsal closure in embryogenesis (Gallo and Johnson, 2002).…”

Section: Rhoa Is Required For the Activation Of Jnk By Wnt/ Pcp Pathwmentioning

confidence: 99%

See 1 more Smart Citation

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

Kim

Han

2005

Developmental Dynamics

105

View full text Add to dashboard Cite

The Wnt/planar cell polarity (PCP) pathway plays a critical role in wing, eye, and sensory bristle development of Drosophila and in convergent extension (CE) movements during vertebrate gastrulation. In Drosophila, Jun N-terminal kinase (JNK) and Rho-associated kinase (ROK) participate in RhoA-mediated PCP pathway during eye and wing development. In mammalian cells, Rac1 and Cdc42 but not RhoA are required for JNK activation by Wnt/PCP signals. However, there has been no evidence that Rho GTPases regulate JNK activation in Wnt/PCP pathway during Xenopus CE movements. Here, we report that Xenopus RhoA (XRhoA), but not Xenopus Cdc42 (XCdc42), is essential for JNK activation downstream of the Wnt/PCP pathway during Xenopus CE movements, and the phenotypic effect of loss of XRhoA function was rescued by Xenopus JNK1 (XeJNK1). In addition, XRhoA rescues the inhibition of CE movements by the DEP domain deletion mutant of Xenopus Dsh (Xdsh-⌬DEP), which has dominant negative (DN) effects on JNK activation, and the PDZ domain deletion mutant of Xdsh (Xdsh-⌬PDZ). Moreover, we demonstrate that Xenopus Rho-associated kinase ␣ (xROK␣), which is expressed mainly in mesoderm and ectoderm that undergo extensive cell rearrangements, regulates CE movements without affecting gene expression, and injection of xROK␣ rescued the inhibition of CE movements caused by DN XRhoA. Finally, we show that ROK␣ and JNK synergistically rescued embryos overexpressing DN XRhoA, which exhibit gastrulation defects, although ROK␣ is not required for JNK activation. Together, these data suggest that JNK and ROK␣ function in the noncanonical Wnt/RhoA pathway to regulate Xenopus CE movements. Developmental Dynamics 232: 958 -968, 2005.

show abstract

Mixed-lineage kinase control of JNK and p38 MAPK pathways

Cited by 537 publications

References 108 publications

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

Inhibition of membrane depolarisation-induced transcriptional activity of cyclic AMP response element binding protein (CREB) by the dual-leucine-zipper-bearing kinase in a pancreatic islet beta cell line

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

Contact Info

Product

Resources

About