Top ▲

TAO kinase 1

Click here for help

Target id: 2233

Nomenclature: TAO kinase 1

Abbreviated Name: TAO1

Family: TAO subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1001 17q11.2 TAOK1 TAO kinase 1
Mouse - 1001 11 B5 Taok1 TAO kinase 1
Rat - 1001 10q24 Taok1 TAO kinase 1
Previous and Unofficial Names Click here for help
MAP3K16 | MARKK | prostate-derived sterile 20 (Ste20)-like kinase 2 | PSK2 | thousand and one amino acid protein 1 | thousand and one kinase 1
Database Links Click here for help
Alphafold Q7L7X3 (Hs), Q5F2E8 (Mm), O88664 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5261 (Hs)
Ensembl Gene ENSG00000160551 (Hs), ENSMUSG00000017291 (Mm), ENSRNOG00000015692 (Rn)
Entrez Gene 57551 (Hs), 216965 (Mm), 286993 (Rn)
Human Protein Atlas ENSG00000160551 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:57551 (Hs), mmu:216965 (Mm), rno:286993 (Rn)
OMIM 610266 (Hs)
Pharos Q7L7X3 (Hs)
RefSeq Nucleotide NM_020791 (Hs), NM_144825 (Mm), NM_173327 (Rn)
RefSeq Protein NP_065842 (Hs), NP_659074 (Mm), NP_775449 (Rn)
UniProtKB Q7L7X3 (Hs), Q5F2E8 (Mm), O88664 (Rn)
Wikipedia TAOK1 (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AMG28 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 4
⤷ pIC50 7.7 (IC50 2x10-8 M) [4]
compound 18 [PMID: 20873740] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 6
⤷ pIC50 6.4 (IC50 4.2x10-7 M) [6]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: TAOK1
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.6 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: TAO1/TAOK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.9 0.0 0.5
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.3 0.0 1.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 18.8 15.0 4.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 22.6 8.0 2.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 26.0 5.0 3.0
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 28.9
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 37.5 11.0 0.0
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 41.9 34.0 8.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 43.9 7.0 10.0
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
TAOK1 has been discovered to function as a negative regulator of IL-17 (IL-17A)-mediated signal transduction and inflammation [9]. IL-17 is a proinflammatory cytokine involved in the development of several autoimmune diseases, including inflammatory bowel disease and Sjögren's syndrome. TAOK1 appears to interact with IL-17RA, and this action prevents IL-17RA-Act1-TRAF6 signaling complex formation, and inhibits NF-κB and MAP kinase pathway activation. This in turn leads to a reduction in the expression of IL-17-induced proinflammatory mediators (e.g. IL-6, CXCL1, CXCL2, CCL20 and CSF3). TAOK1 is revealed as a component of the regulatory system that controls IL-17activity that is necessary to limit harmful IL-17-driven inflammation and autoimmune disease. Decreased TAOK1 expression has been reported in the colons of ulcerative colitis patients. Thus, the accumulating evidence delineating TAOK1 's functions indicate that this kinase is involved in the pathogenesis of IL-17-related autoimmune conditions.
Physiological Consequences of Altering Gene Expression Click here for help
Taok1-deficient mice are more sensitive to TNBS-induced inflammatory bowel disease (IBD) than wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Conditional knockout by crossing Taok1fl/fl mice with Pvillin-Cre transgenic mice to generate with Taok1 deletion specifically in intestinal epithelial cells.
References:  9
Overexpression of TAOK1 in HeLa cells downregulates IL-17-induced phosphorylation of NF-&kapp;B and MAPK kinases (i.e. TAOK1 inhibits the IL-17 signaling pathway).
Species:  Human
Tissue:  HeLa cells.
Technique:  Transient expression.
References:  9
General Comments
As well as being a member of the STE20-like kinases family, TAOK1 is also a member of the MAP kinase kinase kinase family, and is involved in MAPK signaling. It is reported to be involved in microtubule dynamics and mitotic progression [3], and the p38 and JNK response to DNA damage and stress stimuli [7].

References

Show »

1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

3. Draviam VM, Stegmeier F, Nalepa G, Sowa ME, Chen J, Liang A, Hannon GJ, Sorger PK, Harper JW, Elledge SJ. (2007) A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling. Nat Cell Biol, 9 (5): 556-64. [PMID:17417629]

4. Drewry DH, Potjewyd FM, Bayati A, Smith JL, Dickmander RJ, Howell S, Taft-Benz S, Min SM, Hossain MA, Heise M et al.. (2022) Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses. J Med Chem, 65 (19): 12860-12882. [PMID:36111834]

5. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

6. Menichincheri M, Albanese C, Alli C, Ballinari D, Bargiotti A, Caldarelli M, Ciavolella A, Cirla A, Colombo M, Colotta F et al.. (2010) Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding. J Med Chem, 53 (20): 7296-315. [PMID:20873740]

7. Raman M, Earnest S, Zhang K, Zhao Y, Cobb MH. (2007) TAO kinases mediate activation of p38 in response to DNA damage. EMBO J, 26 (8): 2005-14. [PMID:17396146]

8. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

9. Zhang Z, Tang Z, Ma X, Sun K, Fan L, Fang J, Pan J, Wang X, An H, Zhou J. (2018) TAOK1 negatively regulates IL-17-mediated signaling and inflammation. Cell Mol Immunol, 15 (8): 794-802. [PMID:29400705]

How to cite this page

TAO subfamily: TAO kinase 1. Last modified on 23/01/2024. Accessed on 10/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2233.