serine/threonine kinase 11

Target id: 2212

Nomenclature: serine/threonine kinase 11

Abbreviated Name: LKB1

Family: LKB subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     serine/threonine kinase 11 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 433 19p13.3 STK11 serine/threonine kinase 11
Mouse - 436 10 C1 Stk11 serine/threonine kinase 11
Rat - 436 7 q11 Stk11 serine/threonine kinase 11
Previous and Unofficial Names
liver kinase B1 homolog | Par-4 | PJS | polarization-related protein LKB1 | serine/threonine kinase 11 (Peutz-Jeghers syndrome)
Database Links
BRENDA
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the heterotrimeric IKB1-STRADalpha-MO25alpha complex.
PDB Id:  2WTK
Resolution:  2.65Å
Species:  Human
References:  8
Enzyme Reaction
EC Number: 2.7.11.1
DiscoveRx KINOMEscan® screen
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: 2,6

Key to terms and symbols Click column headers to sort
Target used in screen: LKB1
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 7.4 pKd
lestaurtinib Hs Inhibitor Inhibition 7.2 pKd
staurosporine Hs Inhibitor Inhibition 7.2 pKd
KW-2449 Hs Inhibitor Inhibition 6.6 pKd
fedratinib Hs Inhibitor Inhibition 6.5 pKd
midostaurin Hs Inhibitor Inhibition 6.5 pKd
SU-14813 Hs Inhibitor Inhibition 6.4 pKd
tozasertib Hs Inhibitor Inhibition 5.9 pKd
PHA-665752 Hs Inhibitor Inhibition 5.6 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
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: 1,3

Key to terms and symbols Click column headers to sort
Target used in screen: LKB1/LKB1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
indirubin derivative E804 Hs Inhibitor Inhibition 5.8 30.0 3.0
TWS119 Hs Inhibitor Inhibition 12.4 67.0 11.0
PKR inhibitor Hs Inhibitor Inhibition 13.5 21.0 1.0
staurosporine Hs Inhibitor Inhibition 18.7 77.0 20.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 23.5 87.0 41.0
indirubin-3'-monoxime Hs Inhibitor Inhibition 25.6 83.0 44.0
Gö 6976 Hs Inhibitor Inhibition 31.8 82.0 96.0
aloisine A Hs Inhibitor Inhibition 33.5 97.0 73.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 34.8 90.0 55.0
K-252a Hs Inhibitor Inhibition 41.4 97.0 74.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Development of fatal TH2-dominant inflammatory symptoms in mice with a specific Stk11 knockout in their Treg cells, and experiments showing Stk11's role in the coordination of metabolic and functional fitness of Treg cells, suggest that this kinase acts as a crucial checkpoint that actively maintains Treg cell survival and homeostatic function [4,7]. Stk11 was found to control Treg expression of the T cell co-receptors PD-1, GITR and OX40 (expression elevated in the absence of Stk11).
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045059 positive thymic T cell selection IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0050852 T cell receptor signaling pathway IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045059 positive thymic T cell selection IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045059 positive thymic T cell selection IEA
GO:0050852 T cell receptor signaling pathway IEA
Clinically-Relevant Mutations and Pathophysiology
Disease:  Melanoma, cutaneous malignant, susceptibility to, 1; CMM1
OMIM: 155600
Disease:  Pancreatic cancer
Disease Ontology: DOID:1793
OMIM: 260350
Disease:  Peutz-Jeghers syndrome
Disease Ontology: DOID:3852
OMIM: 175200
Orphanet: ORPHA2869
Disease:  Testicular germ cell tumor
Synonyms: Seminoma [Disease Ontology: DOID:4440]
Testicular pure germ cell tumor [Disease Ontology: DOID:4087]
Disease Ontology: DOID:4440, DOID:4087
OMIM: 273300
General Comments
LKB1 (encoded by STK11), via direct phosphorylation of AMPK, functions as a bioenergetic sensor that controls cell metabolism and growth, and acts as a tumour suppressor [5].

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. 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]

4. He N, Fan W, Henriquez B, Yu RT, Atkins AR, Liddle C, Zheng Y, Downes M, Evans RM. (2017) Metabolic control of regulatory T cell (Treg) survival and function by Lkb1. Proc. Natl. Acad. Sci. U.S.A.,  [Epub ahead of print]. [PMID:29109251]

5. Shackelford DB, Shaw RJ. (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer9 (8): 563-75. [PMID:19629071]

6. 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]

7. Yang K, Blanco DB, Neale G, Vogel P, Avila J, Clish CB, Wu C, Shrestha S, Rankin S, Long L et al.. (2017) Homeostatic control of metabolic and functional fitness of Treg cells by LKB1 signalling. Nature,  [Epub ahead of print]. [PMID:28847007]

8. Zeqiraj E, Filippi BM, Deak M, Alessi DR, van Aalten DM. (2009) Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Science326 (5960): 1707-11. [PMID:19892943]

How to cite this page

LKB subfamily: serine/threonine kinase 11. Last modified on 14/11/2017. Accessed on 21/04/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2212.