The TAK1–NLK–MAPK-related pathway antagonizes signalling between β-catenin and transcription factor TCF

In the citing paper

“Thus, the effect of mammalian NLK on Wnt signaling seems to depend on the cell type; NLK plays some suppressive role in Wnt signaling in 29317) and DLD-1 cell lines30) and a positive role in SaOS-2, NB39-nu and Nh12 cell lines (the present study).”

In the citing paper

“In 293 cells, Flag-NLK suppressed reporter gene expression, a finding in agreement with previous reports.17), 34)”

In the citing paper

“Ishitani et al. correspondingly reported that NLK could suppress the transcriptional activity of the β-catenin-TCF complex through phosphorylation of TCF in human 293 cells.17)”

In the citing paper

“Ishitani et al. suggested that DNA binding of LEF1 decreased with its phosphorylation at threonine 155 and serine 166 by overexpression of NLK.17), 34)”

In the citing paper

“Active NLK phosphorylates LEF-1/TCF and prevents the β-catenin-TCF complex from binding to DNA, thereby inhibiting the ability of β-catenin-TCF to activate transcription.”

In the citing paper

“TAK1 functions upstream of NLK and enhances NLK kinase activity.”

In the citing paper

“Recent evidence indicates that the Wnt signaling pathway in mammalian cells is also regulated by a MAPK-related pathway composed of MAPK kinase kinase TAK1 and MAPK-related NLK (13).”

In the citing paper

“Consistent with this, ectopic expression of NLK blocks double-axis formation in Xenopus induced by overexpression of β-catenin but not by the downstream components siamois and twin (13).”

In the citing paper

“We have previously shown that NLK interacts with the β-catenin-LEF-1/TCF complex (13).”

In the citing paper

“As observed previously (13), NLK phosphorylated TCF-4 in vitro even in the absence of β-catenin transfection (Fig. 2, bottom panel, lane 4).”

In the citing paper

“We have previously shown that NLK associates with TCF-4 (13).”

In the citing paper

“These mobility shifts were shown to be due to phosphorylation (13).”

In the citing paper

“We have previously shown that NLK phosphorylates TCF-4 and prevents the β-catenin-TCF-4 complex from binding DNA (13).”

In the citing paper

“Thus, as observed previously (13), NLK phosphorylation of TCF-4 prevents the β-catenin-TCF-4 complex from binding DNA.”

In the citing paper

“and thereby inhibits β-catenin-mediated transcription through LEF-1/TCF-binding sites in Wnt pathway-responsive promoters.”

In the citing paper

“This phosphorylation does not disrupt the formation of a complex between LEF-1/TCF and β-catenin”

In the citing paper

“In vivo, coinjection of NLK RNA into early Xenopus embryos results in the inhibition of double-axis formation by β-catenin.”

In the citing paper

“yet it does prevent DNA binding of the β-catenin-TCF-4 complex”

In the citing paper

“Mechanistically, NLK directly interacts with and phosphorylates TCF-4.”

In the citing paper

“Furthermore, in both C. elegans and mammalian cells, the Nemo-like kinases LIT-1 and NLK, respectively, phosphorylate LEF-1/TCF.”

In the citing paper

“Phosphorylation inhibits LEF-1/TCF signaling by disruption of DNA binding (13)”

In the citing paper

“We have previously demonstrated that NLK can regulate the transcriptional activity of a β-catenin-LEF-1/TCF complex (13).”

In the citing paper

“This phosphorylation prevents DNA binding of the β-catenin-TCF4 complex and limits β-catenin-mediated target gene transcription through TCF/LEF [16,17].”

In the citing paper

“Previous studies showed that NLK can regulate the transcriptional activity of the β-catenin-LEF/TCF complex by directly phosphorylating TCF4.”

In the citing paper

“In vertebrates, NLK is considered to be a negative regulator of the Wnt signalling pathway.”

In the citing paper

“Across species, NLK proteins function as important regulators of cell growth, patterning, and death by controlling diverse signaling pathways including Wnt and Notch pathways (Ishitani et al., 1999; Meneghini et al., 1999; Rocheleau et al., 1999; Verheyen et al., 2001; Rottinger et al., 2006).”

In the citing paper

“CamK11 has also been shown to activate TGFβ activated kinase (TAK1) and Nemo-like kinase (NLK) which can antagonize β-catenin/TCF signaling.99”