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| | <StructureSection load='6mrp' size='340' side='right'caption='[[6mrp]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6mrp' size='340' side='right'caption='[[6mrp]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6mrp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MRP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mrp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MRP FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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]] 2.403Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIK3R1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></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=6mrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mrp OCA], [http://pdbe.org/6mrp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mrp RCSB], [http://www.ebi.ac.uk/pdbsum/6mrp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mrp ProSAT]</span></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=6mrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mrp OCA], [https://pdbe.org/6mrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mrp RCSB], [https://www.ebi.ac.uk/pdbsum/6mrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mrp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN]] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). | + | [https://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Anderson, D H]] | + | [[Category: Anderson DH]] |
| - | [[Category: Marshall, J D]] | + | [[Category: Marshall JD]] |
| - | [[Category: Moore, S A]] | + | [[Category: Moore SA]] |
| - | [[Category: Gap protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Signalling protein]]
| + | |
| Structural highlights
Function
P85A_BOVIN Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).
Publication Abstract from PubMed
The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in regulating cell growth and cell survival and is frequently deregulated in cancer cells. p85alpha regulates the p110alpha lipid kinase, and also stabilizes and stimulates PTEN, the lipid phosphatase that downregulates this pathway. In this report, we determined that the p85alpha BH domain binds several phosphorylated phosphoinositide lipids, an interaction that could help localize p85alpha to membranes rich in these lipids. We also identified key residues responsible for mediating PTEN - p85alpha complex formation. Based on these experimental results, a docking model for the PTEN - p85alpha BH domain complex was developed that is consistent with the known binding interactions for both PTEN and p85alpha. This model involves extensive side-chain and peptide backbone contacts between both the PASE and C2 domains of PTEN with the p85alpha BH domains. The p85alpha BH domain residues shown to be important for PTEN binding were p85alpha residues E212, Q221, K225, R228 and H234. We also verified experimentally the importance of PTEN-E91 in mediating the interaction with the p85alpha BH domain. These results shed new light on the mechanism of PTEN regulation by p85alpha.
Insight into the PTEN - p85alpha interaction and lipid binding properties of the p85alpha BH domain.,Marshall JDS, Mellor P, Ruan X, Whitecross DE, Moore SA, Anderson DH Oncotarget. 2018 Dec 11;9(97):36975-36992. doi: 10.18632/oncotarget.26432., eCollection 2018 Dec 11. PMID:30651929[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Marshall JDS, Mellor P, Ruan X, Whitecross DE, Moore SA, Anderson DH. Insight into the PTEN - p85alpha interaction and lipid binding properties of the p85alpha BH domain. Oncotarget. 2018 Dec 11;9(97):36975-36992. doi: 10.18632/oncotarget.26432., eCollection 2018 Dec 11. PMID:30651929 doi:http://dx.doi.org/10.18632/oncotarget.26432
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