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| | ==Crystal structure of sterile 20-like kinase 3 (MST3, STK24) in complex with staurosporine== | | ==Crystal structure of sterile 20-like kinase 3 (MST3, STK24) in complex with staurosporine== |
| - | <StructureSection load='3ckx' size='340' side='right' caption='[[3ckx]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3ckx' size='340' side='right'caption='[[3ckx]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ckx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CKX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CKX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ckx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CKX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ckw|3ckw]]</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ckx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ckx OCA], [https://pdbe.org/3ckx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ckx RCSB], [https://www.ebi.ac.uk/pdbsum/3ckx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ckx ProSAT], [https://www.topsan.org/Proteins/NYSGXRC/3ckx TOPSAN]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STK24, MST3, STK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ckx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ckx OCA], [http://pdbe.org/3ckx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ckx RCSB], [http://www.ebi.ac.uk/pdbsum/3ckx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ckx ProSAT], [http://www.topsan.org/Proteins/NYSGXRC/3ckx TOPSAN]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/STK24_HUMAN STK24_HUMAN]] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.<ref>PMID:16314523</ref> <ref>PMID:17046825</ref> <ref>PMID:19604147</ref> <ref>PMID:19855390</ref> <ref>PMID:19782762</ref> | + | [https://www.uniprot.org/uniprot/STK24_HUMAN STK24_HUMAN] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.<ref>PMID:16314523</ref> <ref>PMID:17046825</ref> <ref>PMID:19604147</ref> <ref>PMID:19855390</ref> <ref>PMID:19782762</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Antonysamy, S S]] | + | [[Category: Antonysamy SS]] |
| - | [[Category: Buchanan, S]] | + | [[Category: Buchanan S]] |
| - | [[Category: Burley, S K]] | + | [[Category: Burley SK]] |
| - | [[Category: Chau, F]] | + | [[Category: Chau F]] |
| - | [[Category: Feil, I]] | + | [[Category: Feil I]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sauder JM]] |
| - | [[Category: Sauder, J M]] | + | [[Category: Wu L]] |
| - | [[Category: Wu, L]] | + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Mst3]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: NYSGXRC, New York SGX Research Center for Structural Genomics]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Staurosporine]]
| + | |
| - | [[Category: Sterile 20-like kinase]]
| + | |
| - | [[Category: Stk24]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
STK24_HUMAN Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Stegert MR, Hergovich A, Tamaskovic R, Bichsel SJ, Hemmings BA. Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Mol Cell Biol. 2005 Dec;25(24):11019-29. PMID:16314523 doi:10.1128/MCB.25.24.11019-11029.2005
- ↑ Lu TJ, Lai WY, Huang CY, Hsieh WJ, Yu JS, Hsieh YJ, Chang WT, Leu TH, Chang WC, Chuang WJ, Tang MJ, Chen TY, Lu TL, Lai MD. Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST. J Biol Chem. 2006 Dec 15;281(50):38405-17. Epub 2006 Oct 17. PMID:17046825 doi:10.1074/jbc.M605035200
- ↑ Chen CB, Ng JK, Choo PH, Wu W, Porter AG. Mammalian sterile 20-like kinase 3 (MST3) mediates oxidative-stress-induced cell death by modulating JNK activation. Biosci Rep. 2009 Sep 16;29(6):405-15. doi: 10.1042/BSR20090096. PMID:19604147 doi:10.1042/BSR20090096
- ↑ Lorber B, Howe ML, Benowitz LI, Irwin N. Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways. Nat Neurosci. 2009 Nov;12(11):1407-14. doi: 10.1038/nn.2414. Epub 2009 Oct 25. PMID:19855390 doi:10.1038/nn.2414
- ↑ Lin CY, Wu HY, Wang PL, Yuan CJ. Mammalian Ste20-like protein kinase 3 induces a caspase-independent apoptotic pathway. Int J Biochem Cell Biol. 2010 Jan;42(1):98-105. doi:, 10.1016/j.biocel.2009.09.012. Epub 2009 Sep 25. PMID:19782762 doi:10.1016/j.biocel.2009.09.012
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