p21 (RAC1) activated kinase 2 | PAKA subfamily | IUPHAR Guide to IMMUNOPHARMACOLOGY

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p21 (RAC1) activated kinase 2

  Target has curated data in GtoImmuPdb

Target id: 2134

Nomenclature: p21 (RAC1) activated kinase 2

Abbreviated Name: PAK2

Family: PAKA 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 - 524 3q29 PAK2 p21 (RAC1) activated kinase 2
Mouse - 524 16 B2 Pak2 p21 (RAC1) activated kinase 2
Rat - 524 11 q22 Pak2 p21 (RAC1) activated kinase 2
Previous and Unofficial Names
gamma-PAK | p21 (CDKN1A)-activated kinase 2 | p21-activated kinase 2 | PAK65 | S6/H4 kinase | p21 protein (Cdc42/Rac)-activated kinase 2
Database Links
BRENDA
CATH/Gene3D
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:  Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex
PDB Id:  3PCS
Resolution:  2.86Å
Species:  Human
References:  10
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 Affinity Parameter Reference
staurosporine Hs Inhibition 9.0 pIC50 6
pIC50 9.0 (IC50 1x10-9 M) [6]
PQA-18 Hs Inhibition 8.0 pIC50 9
pIC50 8.0 (IC50 1x10-8 M) [9]
Description: Using immunoprecipitated PAK2 and histone H4 substrate from Jurkat cells.
FRAX597 Hs Inhibition 7.9 pIC50 8
pIC50 7.9 (IC50 1.3x10-8 M) [8]
FRAX486 Hs Inhibition 7.4 pIC50 4
pIC50 7.4 (IC50 3.95x10-8 M) [4]
Il-94 Hs Inhibition 7.2 pIC50 1
pIC50 7.2 (IC50 6.41x10-8 M) [1]
PF-3758309 Hs Inhibition 6.7 pIC50 7
pIC50 6.7 (IC50 1.9x10-7 M) [7]
compound 4 [PMID: 24432870] Hs Inhibition 6.0 pIC50 7
pIC50 6.0 (IC50 9.7x10-7 M) [7]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
compound 3 [PMID: 26191365] Hs Negative 6.4 pKd 7
pKd 6.4 (Kd 4x10-7 M) [7]
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: 3,11

Key to terms and symbols Click column headers to sort
Target used in screen: PAK2
Ligand Sp. Type Action Affinity Parameter
staurosporine Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Hs Inhibitor Inhibition 7.4 pKd
neratinib Hs Inhibitor Inhibition 7.1 pKd
GSK690693 Hs Inhibitor Inhibition 6.6 pKd
tamatinib Hs Inhibitor Inhibition 6.5 pKd
A-674563 Hs Inhibitor Inhibition 5.8 pKd
bosutinib Hs Inhibitor Inhibition 5.7 pKd
KW-2449 Hs Inhibitor Inhibition 5.6 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin 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: 2,5

Key to terms and symbols Click column headers to sort
Target used in screen: PAK2/PAK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.7 5.5 -0.5
K-252a Hs Inhibitor Inhibition 7.5 19.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 26.4 47.0 7.0
alsterpaullone Hs Inhibitor Inhibition 41.0 43.0 30.0
SB 218078 Hs Inhibitor Inhibition 43.9 91.0 101.0
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 55.6 62.0 37.0
TGF-beta RI kinase inhibitor Hs Inhibitor Inhibition 57.0 107.0 88.0
AG 9 Hs Inhibitor Inhibition 58.1 106.0 99.0
Syk inhibitor II Hs Inhibitor Inhibition 58.9 101.0 83.0
semaxanib Hs Inhibitor Inhibition 66.5 108.0 111.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Pharmacological inhibition of PAK2 has immunosuppressive effects [9].
Immuno Process Associations
Immuno Process:  Inflammation
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 1 GO processes
GO:0035722 interleukin-12-mediated signaling pathway TAS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0031295 T cell costimulation TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0031295 T cell costimulation TAS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0050852 T cell receptor signaling pathway TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0031295 T cell costimulation TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 4 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0031295 T cell costimulation TAS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0050852 T cell receptor signaling pathway TAS

References

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1. Abdel-Magid AF. (2013) PAK1: A Therapeutic Target for Cancer Treatment. ACS Med Chem Lett, 4 (5): 431-2. [PMID:24900689]

2. 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]

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. Dolan BM, Duron SG, Campbell DA, Vollrath B, Shankaranarayana Rao BS, Ko HY, Lin GG, Govindarajan A, Choi SY, Tonegawa S. (2013) Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc. Natl. Acad. Sci. U.S.A., 110 (14): 5671-6. [PMID:23509247]

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. 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]

7. Karpov AS, Amiri P, Bellamacina C, Bellance MH, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I et al.. (2015) Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. ACS Med Chem Lett, 6 (7): 776-81. [PMID:26191365]

8. Licciulli S, Maksimoska J, Zhou C, Troutman S, Kota S, Liu Q, Duron S, Campbell D, Chernoff J, Field J et al.. (2013) FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J. Biol. Chem., 288 (40): 29105-14. [PMID:23960073]

9. Ogura M, Kikuchi H, Suzuki T, Yamaki J, Homma MK, Oshima Y, Homma Y. (2016) Prenylated quinolinecarboxylic acid derivative suppresses immune response through inhibition of PAK2. Biochem. Pharmacol., 105: 55-65. [PMID:26827943]

10. Selyunin AS, Sutton SE, Weigele BA, Reddick LE, Orchard RC, Bresson SM, Tomchick DR, Alto NM. (2011) The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold. Nature, 469 (7328): 107-11. [PMID:21170023]

11. 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

PAKA subfamily: p21 (RAC1) activated kinase 2. Last modified on 15/02/2017. Accessed on 25/03/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2134.