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| | ==Auto-inhibition and phosphorylation-induced activation of PLC-gamma isozymes== | | ==Auto-inhibition and phosphorylation-induced activation of PLC-gamma isozymes== |
| - | <StructureSection load='4k44' size='340' side='right' caption='[[4k44]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4k44' size='340' side='right'caption='[[4k44]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k44]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K44 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k44]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K44 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gqi|3gqi]], [[4k45|4k45]]</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]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Plcg1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=4k44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k44 OCA], [https://pdbe.org/4k44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k44 RCSB], [https://www.ebi.ac.uk/pdbsum/4k44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k44 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] </span></td></tr>
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| - | <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=4k44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k44 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k44 RCSB], [http://www.ebi.ac.uk/pdbsum/4k44 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLCG1_RAT PLCG1_RAT]] Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration (By similarity). | + | [https://www.uniprot.org/uniprot/PLCG1_RAT PLCG1_RAT] Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4k44" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phospholipase C|Phospholipase C]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Phosphoinositide phospholipase C]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Hajicek, N]] | + | [[Category: Hajicek N]] |
| - | [[Category: Sondek, J]] | + | [[Category: Sondek J]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Plc-gamma1]]
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| - | [[Category: Sh2 domain]]
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| Structural highlights
Function
PLCG1_RAT Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration (By similarity).
Publication Abstract from PubMed
Multiple extracellular stimuli, such as growth factors and antigens, initiate signaling cascades through tyrosine phosphorylation and activation of phospholipase C (PLC)-gamma isozymes. Like most other PLCs, PLC-gamma1 is basally auto-inhibited by its X-Y linker, which separates the X- and Y-boxes of the catalytic core. The C-terminal SH2 (cSH2) domain within the X-Y linker is the critical determinant for auto-inhibition of phospholipase activity. Release of auto-inhibition requires an intramolecular interaction between the cSH2 domain and a phosphorylated tyrosine, Tyr783, also located within the X-Y linker. The molecular mechanisms that mediate auto-inhibition and phosphorylation-induced activation have not been defined. Here, we describe structures of the cSH2 domain both alone and bound to a PLC-gamma1 peptide encompassing phosphorylated Tyr783. The cSH2 domain remains largely unaltered by peptide engagement. Point mutations in the cSH2 domain located at the interface with the peptide were sufficient to constitutively activate PLC-gamma1 suggesting that peptide engagement directly interferes with the capacity of the cSH2 domain to block the lipase active site. This idea is supported by mutations in a complimentary surface of the catalytic core that also enhanced phospholipase activity.
Auto-inhibition and phosphorylation-induced activation of PLC-gamma isozymes.,Hajicek N, Charpentier TH, Rush JR, Harden TK, Sondek JE Biochemistry. 2013 Jun 18. PMID:23777354[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hajicek N, Charpentier TH, Rush JR, Harden TK, Sondek JE. Auto-inhibition and phosphorylation-induced activation of PLC-gamma isozymes. Biochemistry. 2013 Jun 18. PMID:23777354 doi:10.1021/bi400433b
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