Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK- SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Note: This description may include information from UniProtKB.
Protein type: CMGC group; EC 18.104.22.168; Kinase, protein; MAPK family; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor); nmo subfamily
Molecular Function: ATP binding; magnesium ion binding; MAP kinase activity; protein binding; protein kinase activity; protein serine/threonine kinase activity; SH2 domain binding; transcription factor binding; ubiquitin protein ligase binding
Biological Process: MAPK cascade; negative regulation of Wnt signaling pathway; peptidyl-threonine phosphorylation; protein amino acid phosphorylation; protein autophosphorylation; protein stabilization; regulation of gene expression; regulation of transcription, DNA-templated; serine phosphorylation of STAT protein; transcription, DNA-dependent; transforming growth factor beta receptor signaling pathway; Wnt receptor signaling pathway, calcium modulating pathway