myosin light chain kinase | Myosin Light Chain Kinase (MLCK) family | IUPHAR/BPS Guide to PHARMACOLOGY

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myosin light chain kinase

Target not currently curated in GtoImmuPdb

Target id: 1552

Nomenclature: myosin light chain kinase

Abbreviated Name: smMLCK

Family: Myosin Light Chain Kinase (MLCK) family

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1914 3q21 MYLK myosin light chain kinase
Mouse - 1950 16 Mylk myosin
Rat - 1961 11q22 Mylk myosin light chain kinase
Previous and Unofficial Names
MLCK108 | MLCK210 | telokin | MLCK1 (smooth muscle and non-muscle isoform) | myosin
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Calmodulin complexed with calmodulin-binding peptide from smooth muscle myosin light chain kinase- solution NMR
PDB Id:  2K0F
Resolution:  0.0Å
Species:  Human
References:  4
Enzyme Reaction
EC Number: 2.7.11.18

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
calmodulin {Sp: Human} Hs Activation - - 5
[5]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RKI-1447 Hs Inhibition 7.8 pIC50 7
pIC50 7.8 (IC50 1.563x10-8 M) [7]
MLCK inhibitor peptide 18 Ggal Inhibition 7.3 pIC50 6
pIC50 7.3 (IC50 5x10-8 M) [6]
View species-specific inhibitor tables
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: 2,8

Key to terms and symbols Click column headers to sort
Target used in screen: MYLK
Ligand Sp. Type Action Value Parameter
GSK-1838705A Hs Inhibitor Inhibition 8.0 pKd
lestaurtinib Hs Inhibitor Inhibition 7.9 pKd
staurosporine Hs Inhibitor Inhibition 7.8 pKd
BI-2536 Hs Inhibitor Inhibition 7.0 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.7 pKd
sunitinib Hs Inhibitor Inhibition 6.6 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.5 pKd
PP-242 Hs Inhibitor Inhibition 6.5 pKd
ruxolitinib Hs Inhibitor Inhibition 6.4 pKd
SU-14813 Hs Inhibitor Inhibition 6.4 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: MLCK/MLCK(MYLK)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 2.2 0.0 0.5
SB 218078 Hs Inhibitor Inhibition 4.0 90.0 65.0
K-252a Hs Inhibitor Inhibition 6.4 1.0 2.0
JAK inhibitor I Hs Inhibitor Inhibition 9.0 2.0 4.0
isogranulatimide Hs Inhibitor Inhibition 15.5 11.0 8.0
SU11652 Hs Inhibitor Inhibition 17.6 9.0 3.0
GF109203X Hs Inhibitor Inhibition 23.2 20.0 7.0
Gö 6976 Hs Inhibitor Inhibition 24.6 16.0 11.0
sunitinib Hs Inhibitor Inhibition 25.6
midostaurin Hs Inhibitor Inhibition 27.3 13.0 10.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Aortic aneurysm, familial thoracic 7; AAT7
Synonyms: Familial thoracic aortic aneurysm and aortic dissection [Orphanet: ORPHA91387]
thoracic aortic aneurysm
Disease Ontology: DOID:14004
OMIM: 613780
Orphanet: ORPHA91387

References

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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. Gsponer J, Christodoulou J, Cavalli A, Bui JM, Richter B, Dobson CM, Vendruscolo M. (2008) A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction. Structure, 16 (5): 736-46. [PMID:18462678]

5. Hathaway DR, Adelstein RS. (1979) Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc. Natl. Acad. Sci. U.S.A., 76 (4): 1653-7. [PMID:156362]

6. Lukas TJ, Mirzoeva S, Slomczynska U, Watterson DM. (1999) Identification of novel classes of protein kinase inhibitors using combinatorial peptide chemistry based on functional genomics knowledge. J. Med. Chem., 42 (5): 910-9. [PMID:10072688]

7. Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM et al.. (2012) Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm, 3 (6): 699-709. [PMID:23275831]

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]

How to cite this page

Myosin Light Chain Kinase (MLCK) family: myosin light chain kinase. Last modified on 03/11/2016. Accessed on 07/04/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1552.