|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Human Mob1-phosphopeptide complex== | | ==Human Mob1-phosphopeptide complex== |
| - | <StructureSection load='4jiz' size='340' side='right' caption='[[4jiz]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4jiz' size='340' side='right'caption='[[4jiz]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jiz]] is a 2 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=4JIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JIZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jiz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JIZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=4jiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jiz OCA], [https://pdbe.org/4jiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jiz RCSB], [https://www.ebi.ac.uk/pdbsum/4jiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jiz ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C2orf6, MOB1, MOB1A, MOB4B, MOBK1B, MOBKL1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4jiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jiz OCA], [http://pdbe.org/4jiz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jiz RCSB], [http://www.ebi.ac.uk/pdbsum/4jiz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jiz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MOB1A_HUMAN MOB1A_HUMAN]] Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.<ref>PMID:15197186</ref> <ref>PMID:18362890</ref> <ref>PMID:19739119</ref> | + | [https://www.uniprot.org/uniprot/MOB1A_HUMAN MOB1A_HUMAN] Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.<ref>PMID:15197186</ref> <ref>PMID:18362890</ref> <ref>PMID:19739119</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Amon, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Lim, D]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Ogrodowicz, R W]] | + | [[Category: Amon A]] |
| - | [[Category: Rock, J M]] | + | [[Category: Lim D]] |
| - | [[Category: Smerdon, S J]] | + | [[Category: Ogrodowicz RW]] |
| - | [[Category: Stach, L]] | + | [[Category: Rock JM]] |
| - | [[Category: Yaffe, M B]] | + | [[Category: Smerdon SJ]] |
| - | [[Category: Signaling protein]]
| + | [[Category: Stach L]] |
| | + | [[Category: Yaffe MB]] |
| Structural highlights
Function
MOB1A_HUMAN Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.[1] [2] [3]
Publication Abstract from PubMed
Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway known as the Mitotic Exit Network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine/threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.
Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes.,Rock JM, Lim D, Stach L, Ogrodowicz RW, Keck JM, Jones MH, Wong CC, Yates JR 3rd, Winey M, Smerdon SJ, Yaffe MB, Amon A Science. 2013 Apr 11. PMID:23579499[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bichsel SJ, Tamaskovic R, Stegert MR, Hemmings BA. Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by the hMOB1 protein. J Biol Chem. 2004 Aug 20;279(34):35228-35. Epub 2004 Jun 14. PMID:15197186 doi:10.1074/jbc.M404542200
- ↑ Hirabayashi S, Nakagawa K, Sumita K, Hidaka S, Kawai T, Ikeda M, Kawata A, Ohno K, Hata Y. Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1. Oncogene. 2008 Jul 17;27(31):4281-92. doi: 10.1038/onc.2008.66. Epub 2008 Mar 24. PMID:18362890 doi:10.1038/onc.2008.66
- ↑ Chow A, Hao Y, Yang X. Molecular characterization of human homologs of yeast MOB1. Int J Cancer. 2010 May 1;126(9):2079-89. doi: 10.1002/ijc.24878. PMID:19739119 doi:10.1002/ijc.24878
- ↑ Rock JM, Lim D, Stach L, Ogrodowicz RW, Keck JM, Jones MH, Wong CC, Yates JR 3rd, Winey M, Smerdon SJ, Yaffe MB, Amon A. Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes. Science. 2013 Apr 11. PMID:23579499 doi:10.1126/science.1235822
|
