misshapen like kinase 1 | MSN subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

misshapen like kinase 1

Target id: 2103

Nomenclature: misshapen like kinase 1

Abbreviated Name: MINK

Family: MSN subfamily

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

   GtoImmuPdb view: OFF :     misshapen like kinase 1 has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1312 17p13.2 MINK1 misshapen like kinase 1
Mouse - 1337 11 B4 Mink1 misshapen-like kinase 1 (zebrafish)
Rat - 1354 10q24 Mink1 misshapen-like kinase 1
Previous and Unofficial Names
GCK family kinase MiNK | MAP4K6 | MAPK/ERK kinase kinase kinase 6 | MEK kinase kinase 6 | MEKKK 6 | MINK | YSK2 | ZC3
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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 Units Reference
PF-03715455 Hs Inhibition 8.2 pIC50 9
pIC50 8.2 (IC50 6x10-9 M) [9]
pexmetinib Hs Inhibition 7.6 pIC50 2
pIC50 7.6 (IC50 2.6x10-8 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: 4,10

Key to terms and symbols Click column headers to sort
Target used in screen: MINK
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.0 pKd
bosutinib Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Hs Inhibitor Inhibition 8.4 pKd
AST-487 Hs Inhibitor Inhibition 8.1 pKd
dovitinib Hs Inhibitor Inhibition 8.0 pKd
KW-2449 Hs Inhibitor Inhibition 7.6 pKd
sunitinib Hs Inhibitor Inhibition 7.5 pKd
neratinib Hs Inhibitor Inhibition 7.5 pKd
SU-14813 Hs Inhibitor Inhibition 7.2 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.1 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: 1,5

Key to terms and symbols Click column headers to sort
Target used in screen: MINK/MINK(MINK1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 0.4 0.0 1.0
SB 218078 Hs Inhibitor Inhibition 0.9 86.0 71.0
bosutinib Hs Inhibitor Inhibition 1.2
staurosporine Hs Inhibitor Inhibition 1.6 0.5 0.5
dovitinib Hs Inhibitor Inhibition 1.6
JAK3 inhibitor VI Hs Inhibitor Inhibition 1.7 6.0 1.0
Gö 6976 Hs Inhibitor Inhibition 2.5 21.0 16.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 3.1 18.0 2.0
SU11652 Hs Inhibitor Inhibition 4.4 9.0 2.0
Flt-3 inhibitor II Hs Inhibitor Inhibition 9.9 21.0 4.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
MINK promotes the negative selection of autoreactive thymocytes during T cell development, an action that is effected by JNK-mediated apoptosis [8].
General Comments
MINK (MINK1, also known as MAP4K6) is ubiquitously expressed in mice and humans, and is found in most tissues [3,6]. Exogenously expressed MINK activates the JNK pathway and p38 signalling in vitro, and studies in cell lines indicate roles for MINK in the regulation of cytoskeletal reorganisation, cell adhesion, and cell motility (NCK(TNIK)-dependent activities), and neuronal structure and function (via activation of Rap2 (RAP2A), a Ras family GTPase) [7].

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. Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, Giricz O, Sukrithan V, Nwankwo G, Shahnaz S et al.. (2016) Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancer Res., 76 (16): 4841-4849. [PMID:27287719]

3. Dan I, Watanabe NM, Kobayashi T, Yamashita-Suzuki K, Fukagaya Y, Kajikawa E, Kimura WK, Nakashima TM, Matsumoto K, Ninomiya-Tsuji J et al.. (2000) Molecular cloning of MINK, a novel member of mammalian GCK family kinases, which is up-regulated during postnatal mouse cerebral development. FEBS Lett., 469 (1): 19-23. [PMID:10708748]

4. 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]

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. Hu Y, Leo C, Yu S, Huang BC, Wang H, Shen M, Luo Y, Daniel-Issakani S, Payan DG, Xu X. (2004) Identification and functional characterization of a novel human misshapen/Nck interacting kinase-related kinase, hMINK beta. J. Biol. Chem., 279 (52): 54387-97. [PMID:15469942]

7. Hussain NK, Hsin H, Huganir RL, Sheng M. (2010) MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function. J. Neurosci., 30 (44): 14786-94. [PMID:21048137]

8. McCarty N, Paust S, Ikizawa K, Dan I, Li X, Cantor H. (2005) Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nat. Immunol., 6 (1): 65-72. [PMID:15608642]

9. Millan DS, Bunnage ME, Burrows JL, Butcher KJ, Dodd PG, Evans TJ, Fairman DA, Hughes SJ, Kilty IC, Lemaitre A et al.. (2011) Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J. Med. Chem., 54 (22): 7797-814. [PMID:21888439]

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]

How to cite this page

MSN subfamily: misshapen like kinase 1. Last modified on 06/06/2018. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2103.