Summary

Name NLK
Full Name Serine/threonine-protein kinase NLK
Synonyms Nemo-like kinase, Protein LAK1 | LAK1
Primary ID Q9UBE8
Links - -
Type protein
Relations 15
Pathways YAP/TAZ regulation
Function 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. 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. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation YAP1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LEF1 0.751
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation FOXO1 0.601
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation STAT3 0.354
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation RPTOR 0.334
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TCF7L2 0.763
Publications: 2 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation TCF7L2 0.763
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NOTCH1 0.391
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SETDB1/NLK/CHD7 0.423
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png binding NLK 0.36
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TCF4 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation LEF1 0.751
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NLK 0.635
Publications: 1 Organism: Homo Sapiens