NLK
NLK (nemo like kinase) is a serine/threonine-protein kinase of the MAP kinase subfamily that regulates transcription factors involved in cell fate determination. It was previously named nemo-like kinase and is classed by HGNC among the atypical mitogen-activated protein kinases. Browse Assay Genie's current range of NLK research reagents below, or read on for the biology behind the target.
NLK is a serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. It acts as a positive effector of non-canonical Wnt signalling, downstream of WNT5A, MAP3K7/TAK1 and HIPK2, and as a negative regulator of canonical Wnt/beta-catenin signalling. It binds and phosphorylates TCF7L2/TCF4 and LEF1, which promotes dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA and the ubiquitination and proteolysis of LEF1, so inhibiting transcription of canonical Wnt target genes.
The kinase also restrains other pathways. It phosphorylates NOTCH1, preventing formation of the transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. It negatively regulates MYB family transcription factors: phosphorylation of MYB leads to its proteolysis, while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Downstream of IL-6 and MAP3K7/TAK1, NLK phosphorylates STAT3, which is in turn required for NLK activation by MAP3K7/TAK1. After an IL-1B stimulus it cooperates with ATF5 to activate C/EBP subfamily members, and it stabilises ATF5 independently of its kinase activity. In response to osmotic stress it inhibits the mTORC1 complex by phosphorylating RPTOR, preventing recruitment of mTORC1 to lysosomes.
The NLK gene encodes a member of the CMGC Ser/Thr protein kinase family, MAP kinase subfamily. NCBI Gene annotates protein serine/threonine kinase activity, DNA-binding transcription factor binding and ubiquitin protein ligase binding, with roles in negative regulation of TORC1 signalling, protein stabilisation and transforming growth factor beta receptor signalling. The protein is found in the nucleus and cytoplasm, and mouse and rat orthologs (Nlk) exist.
NLK switches off canonical Wnt/beta-catenin target gene transcription by phosphorylating TCF7L2/TCF4 and LEF1, and acts downstream of WNT5A in non-canonical signalling.
NLK phosphorylates NOTCH1 and prevents assembly of the active NOTCH1, RBPJ and MAML1 complex, making it a point of Notch control.
NLK phosphorylates RPTOR in response to osmotic stress, keeping mTORC1 from lysosomes and linking the kinase to TORC1 regulation.
NLK works with IL-6/STAT3 and IL-1B/ATF5 signalling and modulates MYB family factors, linking cytokine inputs to transcriptional outputs.
NLK is a serine/threonine kinase that regulates transcription factors controlling cell fate. It inhibits canonical Wnt/beta-catenin signalling by phosphorylating TCF7L2/TCF4 and LEF1, restrains Notch signalling through NOTCH1, targets MYB family members, and inhibits mTORC1 under osmotic stress by phosphorylating RPTOR.
NLK stands for nemo like kinase, previously written nemo-like kinase; UniProt names it serine/threonine-protein kinase NLK. It belongs to the CMGC Ser/Thr protein kinase family, MAP kinase subfamily, and HGNC places it in the atypical mitogen-activated protein kinases. Its EC number is 2.7.11.24.
Yes. The human NLK gene has orthologs named Nlk in both mouse and rat. This allows the kinase to be studied in rodent models, though you should check the datasheet of any product for its validated reactivity.
Wnt, Notch and mTORC1 pathway partners, transcription factors and kinases that act with or are regulated by NLK.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UBE8; product specifications from Assay Genie datasheets.