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Target has curated data in GtoImmuPdb
Target id: 2219
Nomenclature: serine/threonine kinase 3
Abbreviated Name: MST2
Family: MST subfamily
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 491 | 8q22.2 | STK3 | serine/threonine kinase 3 | |
Mouse | - | 497 | 15 B3.1 | Stk3 | serine/threonine kinase 3 | |
Rat | - | 491 | 7q22 | Stk3 | serine/threonine kinase 3 |
Previous and Unofficial Names |
KRS1 | mess1 |
Database Links | |
Alphafold | Q13188 (Hs), Q9JI10 (Mm), O54748 (Rn) |
BRENDA | 2.7.11.1 |
ChEMBL Target | CHEMBL4708 (Hs), CHEMBL4310 (Mm) |
Ensembl Gene | ENSG00000104375 (Hs), ENSMUSG00000022329 (Mm), ENSRNOG00000011278 (Rn) |
Entrez Gene | 6788 (Hs), 56274 (Mm), 65189 (Rn) |
Human Protein Atlas | ENSG00000104375 (Hs) |
KEGG Enzyme | 2.7.11.1 |
KEGG Gene | hsa:6788 (Hs), mmu:56274 (Mm), rno:65189 (Rn) |
OMIM | 605030 (Hs) |
Pharos | Q13188 (Hs) |
RefSeq Nucleotide | NM_001256312 (Hs), NM_019635 (Mm), NM_031735 (Rn) |
RefSeq Protein | NP_006272 (Hs), NP_062609 (Mm), NP_113923 (Rn) |
UniProtKB | Q13188 (Hs), Q9JI10 (Mm), O54748 (Rn) |
Wikipedia | STK3 (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 3,10 |
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Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Target used in screen: MST2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1,6 |
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Target used in screen: MST2/MST2(STK3) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
The kinases MST1 and MST2 are key components of the Hippo signalling pathway. MST1/2 function has been identified as a signal-dependent amplifier of IL-2−STAT5 signalling in Treg cells that maintains immune tolerance, and to be essential for prevention of tumour resistance and autoimmunity [9]. The Hippo pathway, also appears to couple the cellular metabolic state and immune function of CD8α+ dendritic cells, in a mechanism that progammes this dendritic cell subset to present antigens to, and selectively prime CD8+ T cells [4]. In this way, output from the Hippo signalling pathway is able to induce cytotoxic T cell responses to viruses, bacteria and tumours. Manipulating this selective dendritic cell process has implications for cancer immunotherapy, and for treating immune disorders. It can be envisioned that pharmacological agents could be developed which are able to activate CD8α+ dendritic cells, shape the adaptive immune response, and prime anti-tumour T cells. |
Immuno Process Associations | ||
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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. Bata N, Chaikuad A, Bakas NA, Limpert AS, Lambert LJ, Sheffler DJ, Berger LM, Liu G, Yuan C, Wang L et al.. (2022) Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia. J Med Chem, 65 (2): 1352-1369. [PMID:34807584]
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. Du X, Wen J, Wang Y, Karmaus PWF, Khatamian A, Tan H, Li Y, Guy C, Nguyen TM, Dhungana Y et al.. (2018) Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells. Nature, 558 (7708): 141-145. [PMID:29849151]
5. Fan F, He Z, Kong LL, Chen Q, Yuan Q, Zhang S, Ye J, Liu H, Sun X, Geng J et al.. (2016) Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Sci Transl Med, 8 (352): 352ra108. [PMID:27535619]
6. 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]
7. 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]
8. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J Med Chem, 55 (2): 903-13. [PMID:22148921]
9. Shi H, Liu C, Tan H, Li Y, Nguyen TM, Dhungana Y, Guy C, Vogel P, Neale G, Rankin S et al.. (2018) Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R-STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity. Immunity, 49 (5): 899-914.e6. [PMID:30413360]
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]
MST subfamily: serine/threonine kinase 3. Last modified on 24/11/2021. Accessed on 10/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2219.