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5twf

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Revision as of 12:21, 23 September 2020

Regulation of protein interactions by MOB1 phosphorylation

Structural highlights

5twf is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5twg, 5twh
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases MST1 and MST2 and the downstream AGC group kinases LATS1, LATS2, NDR1 and NDR2. Binding of MOB1 to MST1 and MST2 is mediated by its phosphopeptide-binding infrastructure, the specificity of which matches the phosphorylation consensus of MST1 and MST2. On the other hand, binding of MOB1 to the LATS and NDR kinases is mediated by a distinct interaction surface on MOB1. By assembling both upstream and downstream kinases into a single complex, MOB1 facilitates the activation of the latter by the former through a trans-phosphorylation event. Binding of MOB1 to its upstream partners also renders MOB1 a substrate, which serves to differentially regulate its two protein interaction activities (at least in vitro). Our previous interaction proteomics analysis revealed that beyond associating with MST1 (and MST2), MOB1A and MOB1B can associate in a phosphorylation-dependent manner with at least two other signaling complexes, one containing the Rho guanine exchange factors (DOCK6-8) and the other containing the serine/threonine phosphatase PP6. Whether these complexes are recruited through the same mode of interaction as MST1 and MST2 remains unknown. Here, through a comprehensive set of biochemical, biophysical, mutational and structural studies, we quantitatively assess how phosphorylation of MOB1A regulates its interaction with both MST kinases and LATS/NDR family kinases in vitro. Using interaction proteomics, we validate the significance of our in vitro studies and also discover that the phosphorylation-dependent recruitment of PP6 phosphatase and Rho guanine exchange factor protein complexes differ in key respects from that elucidated for MST1 and MST2. Together our studies confirm and extend previous work to delineate the intricate regulatory steps in key signaling pathways.

Regulation of protein interactions by MOB1 phosphorylation.,Xiong S, Couzens AL, Kean MJ, Mao DY, Guettler S, Kurinov I, Gingras AC, Sicheri F Mol Cell Proteomics. 2017 Apr 3. pii: mcp.M117.068130. doi:, 10.1074/mcp.M117.068130. PMID:28373297^[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
↑ Xiong S, Couzens AL, Kean MJ, Mao DY, Guettler S, Kurinov I, Gingras AC, Sicheri F. Regulation of protein interactions by MOB1 phosphorylation. Mol Cell Proteomics. 2017 Apr 3. pii: mcp.M117.068130. doi:, 10.1074/mcp.M117.068130. PMID:28373297 doi:http://dx.doi.org/10.1074/mcp.M117.068130

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5twf"

@@ Line 1: / Line 1: @@
 ==Regulation of protein interactions by MOB1 phosphorylation==
-<StructureSection load='5twf' size='340' side='right' caption='[[5twf]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
+<StructureSection load='5twf' size='340' side='right'caption='[[5twf]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5twf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TWF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TWF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5twf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TWF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TWF 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=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5twg|5twg]], [[5twh|5twh]]</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=5twf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5twf OCA], [http://pdbe.org/5twf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5twf RCSB], [http://www.ebi.ac.uk/pdbsum/5twf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5twf ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5twf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5twf OCA], [http://pdbe.org/5twf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5twf RCSB], [http://www.ebi.ac.uk/pdbsum/5twf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5twf ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Sicheri, F]]
 [[Category: Xiong, S]]

5twf

From Proteopedia

Revision as of 12:21, 23 September 2020

Regulation of protein interactions by MOB1 phosphorylation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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