protein kinase N1 | Protein kinase N (PKN) family | IUPHAR/BPS Guide to PHARMACOLOGY

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protein kinase N1

target has curated data in GtoImmuPdb

Target id: 1520

Nomenclature: protein kinase N1

Abbreviated Name: PKN1

Family: Protein kinase N (PKN) 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 - 942 19p13.12 PKN1 protein kinase N1
Mouse - 946 8 Pkn1 protein kinase N1
Rat - 946 19q11 Pkn1 protein kinase N1
Previous and Unofficial Names
PAK1 | PRK1 | PRKCL1 | protein kinase C-like 1 | protease-activated kinase 1 | protein kinase PKN | Stk3 | DBK | protein kinase C-related kinase 1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF HUMAN RHOA COMPLEXED WITH THE EFFECTOR DOMAIN OF THE PROTEIN KINASE PKN/PRK1
PDB Id:  1CXZ
Resolution:  2.2Å
Species:  Human
References:  6
Enzyme Reaction
EC Number: 2.7.11.13

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
staurosporine Hs Inhibition 9.0 pIC50 3
pIC50 9.0 (IC50 1x10-9 M) [3]
RKI-1447 Hs Inhibition >9.0 pIC50 8
pIC50 >9.0 (IC50 <1x10-9 M) [8]
tofacitinib Hs Inhibition 6.9 pIC50 7
pIC50 6.9 (IC50 1.22x10-7 M) [7]
compound 20 [PMID: 22136433] Hs Inhibition 6.5 pIC50 5
pIC50 6.5 (IC50 3.1x10-7 M) [5]
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: 2,10

Key to terms and symbols Click column headers to sort
Target used in screen: PKN1
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 8.9 pKd
lestaurtinib Hs Inhibitor Inhibition 8.3 pKd
midostaurin Hs Inhibitor Inhibition 8.0 pKd
GSK690693 Hs Inhibitor Inhibition 7.5 pKd
tofacitinib Hs Inhibitor Inhibition 6.8 pKd
dovitinib Hs Inhibitor Inhibition 6.7 pKd
A-674563 Hs Inhibitor Inhibition 6.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.5 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.5 pKd
KW-2449 Hs Inhibitor Inhibition 6.2 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

Key to terms and symbols Click column headers to sort
Target used in screen: nd/PKN1(PRK1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.1
K-252a Hs Inhibitor Inhibition 1.3
midostaurin Hs Inhibitor Inhibition 1.4
SB 218078 Hs Inhibitor Inhibition 2.7
Ro-32-0432 Hs Inhibitor Inhibition 7.1
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 9.7
Gö 6976 Hs Inhibitor Inhibition 10.3
H-89 Hs Inhibitor Inhibition 14.3
JAK3 inhibitor VI Hs Inhibitor Inhibition 14.4
dovitinib Hs Inhibitor Inhibition 15.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [4]. PKN1 also plays a role in germinal center formation, by negatively regulating Akt kinase downstream of the B cell receptor [11], and SNPs in PKN1 (and several other genes) are suggestively associated with the presence of ectopic germinal center-like structures in the minor salivary glands of some patients (25%) with the autoimmune disease, primary Sjögren's syndrome [9].
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:0002634 regulation of germinal center formation IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001783 B cell apoptotic process IEA
GO:0002634 regulation of germinal center formation IEA
GO:0030889 negative regulation of B cell proliferation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001782 B cell homeostasis IEA
GO:0002634 regulation of germinal center formation IEA
GO:0002637 regulation of immunoglobulin production IEA
GO:0030889 negative regulation of B cell proliferation IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0048536 spleen development IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0030889 negative regulation of B cell proliferation IEA

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. Hall MD, Salam NK, Hellawell JL, Fales HM, Kensler CB, Ludwig JA, Szakács G, Hibbs DE, Gottesman MM. (2009) Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells. J. Med. Chem., 52 (10): 3191-204. [PMID:19397322]

4. Haraga A, Miller SI. (2006) A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Cell. Microbiol., 8 (5): 837-46. [PMID:16611232]

5. Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S et al.. (2012) 7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes. J. Med. Chem., 55 (1): 403-13. [PMID:22136433]

6. Maesaki R, Ihara K, Shimizu T, Kuroda S, Kaibuchi K, Hakoshima T. (1999) The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1. Mol. Cell, 4 (5): 793-803. [PMID:10619026]

7. Ostrovskyi D, Rumpf T, Eib J, Lumbroso A, Slynko I, Klaeger S, Heinzlmeir S, Forster M, Gehringer M, Pfaffenrot E et al.. (2016) Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). Future Med Chem, 8 (13): 1537-51. [PMID:27572962]

8. 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]

9. Reksten TR, Johnsen SJ, Jonsson MV, Omdal R, Brun JG, Theander E, Eriksson P, Wahren-Herlenius M, Jonsson R, Nordmark G. (2014) Genetic associations to germinal centre formation in primary Sjogren's syndrome. Ann. Rheum. Dis., 73 (6): 1253-8. [PMID:23606706]

10. 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]

11. Yasui T, Sakakibara-Yada K, Nishimura T, Morita K, Tada S, Mosialos G, Kieff E, Kikutani H. (2012) Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation. Proc. Natl. Acad. Sci. U.S.A., 109 (51): 21022-7. [PMID:23223530]

How to cite this page

Protein kinase N (PKN) family: protein kinase N1. Last modified on 08/03/2017. Accessed on 17/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1520.