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| | <StructureSection load='2aug' size='340' side='right'caption='[[2aug]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='2aug' size='340' side='right'caption='[[2aug]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2aug]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AUG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2aug]] is a 2 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=2AUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AUG FirstGlance]. <br> |
| - | </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=2aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aug OCA], [http://pdbe.org/2aug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aug RCSB], [http://www.ebi.ac.uk/pdbsum/2aug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2aug ProSAT]</span></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]] 2.3Å</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=2aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aug OCA], [https://pdbe.org/2aug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aug RCSB], [https://www.ebi.ac.uk/pdbsum/2aug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aug ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GRB14_HUMAN GRB14_HUMAN]] Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.<ref>PMID:15210700</ref> <ref>PMID:19648926</ref> | + | [https://www.uniprot.org/uniprot/GRB14_HUMAN GRB14_HUMAN] Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.<ref>PMID:15210700</ref> <ref>PMID:19648926</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Daly, R J]] | + | [[Category: Daly RJ]] |
| - | [[Category: Depetris, R S]] | + | [[Category: Depetris RS]] |
| - | [[Category: Gimpelevich, I]] | + | [[Category: Gimpelevich I]] |
| - | [[Category: Holt, L J]] | + | [[Category: Holt LJ]] |
| - | [[Category: Hu, J]] | + | [[Category: Hu J]] |
| - | [[Category: Hubbard, S R]] | + | [[Category: Hubbard SR]] |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| - | [[Category: Signaling protein]]
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| Structural highlights
Function
GRB14_HUMAN Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an intervening stretch of approximately 45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated that Grb14 is a tissue-specific negative regulator of insulin receptor signaling and that inhibition is mediated by the BPS region. We have determined the crystal structure of the Grb14 BPS region in complex with the tyrosine kinase domain of the insulin receptor. The structure reveals that the N-terminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide binding groove of the kinase. Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling.
Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14.,Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ, Hubbard SR Mol Cell. 2005 Oct 28;20(2):325-33. PMID:16246733[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ King CC, Newton AC. The adaptor protein Grb14 regulates the localization of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2004 Sep 3;279(36):37518-27. Epub 2004 Jun 21. PMID:15210700 doi:10.1074/jbc.M405340200
- ↑ Depetris RS, Wu J, Hubbard SR. Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14. Nat Struct Mol Biol. 2009 Aug;16(8):833-9. Epub 2009 Aug 2. PMID:19648926 doi:10.1038/nsmb.1642
- ↑ Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ, Hubbard SR. Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14. Mol Cell. 2005 Oct 28;20(2):325-33. PMID:16246733 doi:10.1016/j.molcel.2005.09.001
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