ribosomal protein S6 kinase A5 | MSK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

ribosomal protein S6 kinase A5

Target not currently curated in GtoImmuPdb

Target id: 1523

Nomenclature: ribosomal protein S6 kinase A5

Abbreviated Name: MSK1

Family: MSK subfamily

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 - 802 14q31-q32.1 RPS6KA5 ribosomal protein S6 kinase A5
Mouse - 863 12 Rps6ka5 ribosomal protein S6 kinase
Rat - 518 6q32 Rps6ka5 ribosomal protein S6 kinase A5
Previous and Unofficial Names
RSK-like protein kinase | ribosomal protein S6 kinase alpha-5 | ribosomal protein S6 kinase, 90kDa, polypeptide 5 | nuclear mitogen- and stress-activated protein kinase 1 | RLPK | ribosomal protein S6 kinase
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the C-terminal kinase domain of MSK1
PDB Id:  3KN6
Resolution:  2.0Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the C-terminal kinase domain of msk1 in complex with AMP-PNP
PDB Id:  3KN5
Ligand:  AMP-PNP
Resolution:  2.4Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  The structure of the N-terminal kinase domain of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein
PDB Id:  1VZO
Resolution:  1.8Å
Species:  Human
References:  6
Enzyme Reaction
EC Number: 2.7.11.1

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SB-747651A Hs Inhibition 9.3 pIC50 2
pIC50 9.3 (IC50 5x10-10 M) [2]
compound 24 [PMID: 15955699] Hs Inhibition 8.9 pIC50 2
pIC50 8.9 (IC50 1.4x10-9 M) [2]
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: 3,7

Key to terms and symbols Click column headers to sort
Target used in screen: RPS6KA5(Kin.Dom.1-N-terminal)
Ligand Sp. Type Action Value Parameter
sunitinib Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Hs Inhibitor Inhibition 7.4 pKd
staurosporine Hs Inhibitor Inhibition 7.4 pKd
SU-14813 Hs Inhibitor Inhibition 6.8 pKd
midostaurin Hs Inhibitor Inhibition 6.6 pKd
enzastaurin Hs Inhibitor Inhibition 6.4 pKd
dovitinib Hs Inhibitor Inhibition 6.2 pKd
AST-487 Hs Inhibitor Inhibition 6.1 pKd
linifanib Hs Inhibitor Inhibition 5.9 pKd
ruboxistaurin Hs Inhibitor Inhibition 5.9 pKd
Target used in screen: RPS6KA5(Kin.Dom.2-C-terminal)
Ligand Sp. Type Action Value Parameter
ruxolitinib Hs Inhibitor Inhibition 6.8 pKd
tamatinib Hs Inhibitor Inhibition 6.8 pKd
GSK690693 Hs Inhibitor Inhibition 6.8 pKd
BI-2536 Hs Inhibitor Inhibition 6.6 pKd
staurosporine Hs Inhibitor Inhibition 6.1 pKd
lestaurtinib Hs Inhibitor Inhibition 6.0 pKd
PHA-665752 Hs Inhibitor Inhibition 6.0 pKd
SU-14813 Hs Inhibitor Inhibition 5.8 pKd
PP-242 Hs Inhibitor Inhibition 5.8 pKd
sunitinib Hs Inhibitor Inhibition 5.8 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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: MSK1/MSK1(RPS6KA5)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 1.2 0.5 -0.5
SB 218078 Hs Inhibitor Inhibition 9.9 41.0 33.0
K-252a Hs Inhibitor Inhibition 12.3 5.0 0.0
midostaurin Hs Inhibitor Inhibition 13.2 13.0 8.0
GF109203X Hs Inhibitor Inhibition 17.0 24.0 4.0
Gö 6976 Hs Inhibitor Inhibition 23.7 3.0 2.0
Ro-32-0432 Hs Inhibitor Inhibition 24.8
PKR inhibitor Hs Inhibitor Inhibition 34.7 43.0 7.0
PKCbeta inhibitor Hs Inhibitor Inhibition 36.9 39.0 6.0
indirubin derivative E804 Hs Inhibitor Inhibition 37.5 47.0 10.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0001818 negative regulation of cytokine production TAS
GO:0070498 interleukin-1-mediated signaling pathway IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS

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. Bamford MJ, Bailey N, Davies S, Dean DK, Francis L, Panchal TA, Parr CA, Sehmi S, Steadman JG, Takle AK et al.. (2005) (1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: further optimisation as highly potent and selective MSK-1-inhibitors. Bioorg. Med. Chem. Lett., 15 (14): 3407-11. [PMID:15955699]

3. 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]

4. 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]

5. Malakhova M, D'Angelo I, Kim HG, Kurinov I, Bode AM, Dong Z. (2010) The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1. J. Mol. Biol., 399 (1): 41-52. [PMID:20382163]

6. Smith KJ, Carter PS, Bridges A, Horrocks P, Lewis C, Pettman G, Clarke A, Brown M, Hughes J, Wilkinson M et al.. (2004) The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein. Structure, 12 (6): 1067-77. [PMID:15274926]

7. 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

MSK subfamily: ribosomal protein S6 kinase A5. Last modified on 30/03/2016. Accessed on 27/05/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1523.