3-phosphoinositide dependent protein kinase-1

Nomenclature: 3-phosphoinositide dependent protein kinase-1

Abbreviated Name: PDK1

Family: PDK1 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 - 556 16p13.3 PDPK1 3-phosphoinositide dependent protein kinase-1
Mouse - 559 17 A3.3 Pdpk1 3-phosphoinositide dependent protein kinase 1
Rat - 559 10q12 Pdpk1 3-phosphoinositide dependent protein kinase-1
Previous and Unofficial Names
3-Phosphoinositide-dependent protein kinase 1
PkB kinase
protein kinase B kinase
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG BRITE Hierarchy
KEGG Gene
OMIM
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  PDK1 in complex with inhibitor MP7
PDB Id:  3NAX
Resolution:  1.75Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  HIGH RESOLUTION CRYSTAL STRUCTURE OF THE HUMAN PDK1 CATALYTIC DOMAIN
PDB Id:  1H1W
Resolution:  2.0Å
Species:  Human
References:  2
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: 3,6

Key to terms and symbols Click column headers to sort
Target used in screen: PDPK1
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.77 pKd
lestaurtinib Hs Inhibitor Inhibition 8.47 pKd
R406 Hs Inhibitor Inhibition 6.92 pKd
midostaurin Hs Inhibitor Inhibition 6.72 pKd
KW-2449 Hs Inhibitor Inhibition 6.19 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.15 pKd
SU-14813 Hs Inhibitor Inhibition 5.59 pKd
SB203580 Hs Inhibitor Inhibition <5.52 pKd
erlotinib Hs Inhibitor Inhibition <5.52 pKd
GSK690693 Hs Inhibitor Inhibition <5.52 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: PDK1/PDK1(PDPK1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 1.6 -1.0 0.0
staurosporine Hs Inhibitor Inhibition 4.4 0.5 0.0
SB 218078 Hs Inhibitor Inhibition 10.6 27.0 4.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 19.3 3.0 0.0
midostaurin Hs Inhibitor Inhibition 21.8 2.0 1.0
JAK inhibitor I Hs Inhibitor Inhibition 27.0 3.0 1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 46.9 6.0 2.0
Gö 6976 Hs Inhibitor Inhibition 63.2 6.0 6.0
Cdk4 inhibitor Hs Inhibitor Inhibition 66.1 75.0 29.0
Cdk2 inhibitor IV Hs Inhibitor Inhibition 69.1 20.0 3.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Biondi RM, Komander D, Thomas CC, Lizcano JM, Deak M, Alessi DR, van Aalten DM. (2002) High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. EMBO J.21 (16): 4219-28. [PMID:12169624]

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. Nagashima K, Shumway SD, Sathyanarayanan S, Chen AH, Dolinski B, Xu Y, Keilhack H, Nguyen T, Wiznerowicz M, Li L et al.. (2011) Genetic and pharmacological inhibition of PDK1 in cancer cells: characterization of a selective allosteric kinase inhibitor. J. Biol. Chem.286 (8): 6433-48. [PMID:21118801]

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]

How to cite this page

PDK1 family: 3-phosphoinositide dependent protein kinase-1. Last modified on 26/03/2013. Accessed on 02/09/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1519.