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5n7g

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Revision as of 08:10, 17 January 2018

MAGI-1 complexed with a synthetic pRSK1 peptide

Structural highlights

5n7g is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Gene:	ANXA2, ANX2, ANX2L4, CAL1H, LPC2D (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MAGI1_HUMAN] May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface (By similarity). [KS6A1_HUMAN] Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11]

Publication Abstract from PubMed

Assembly and disassembly of protein-protein complexes needs to be dynamically controlled and phosphoswitches based upon linear motifs are crucial in this process. Extracellular signal regulated kinase 2 (ERK2) recognizes a linear binding motif at the C-terminal tail (CTT) of ribosomal S6 kinase 1 (RSK1), leading to phosphorylation and subsequent activation of RSK1. The CTT also contains a classical PDZ domain binding motif which binds RSK substrates (e.g. MAGI-1). We show that autophosphorylation of the disordered CTT promotes the formation of an intramolecular charge clamp, which efficiently masks critical residues and indirectly hinders ERK binding. Thus, RSK1 CTT operates as an autoregulated phosphoswitch: its phosphorylation at specific sites affects its protein binding capacity and its conformational dynamics. These biochemical feedbacks, which form the structural basis for the rapid dissociation of ERK2-RSK1 and RSK1-PDZ substrate complexes under sustained epidermal growth factor (EGF) stimulation, were structurally characterized and validated in living cells. Overall, conformational changes induced by phosphorylation in disordered regions of protein kinases, coupled to allosteric events occurring in the kinase domain cores, may provide mechanisms that contribute to the emergence of complex signaling activities. In addition, we show that phosphoswitches based upon linear motifs can be functionally classified as ON and OFF protein-protein interaction switches or dimmers, depending on the specific positioning of phosphorylation target sites in relation to functional linear binding motifs. Moreover, interaction of phosphorylated residues with positively-charged residues in disordered regions is likely to be a common mechanism of phosphoregulation. This article is protected by copyright. All rights reserved.

Dynamic control of RSK complexes by phosphoswitch-based regulation.,Gogl G, Biri-Kovacs B, Poti AL, Vadaszi H, Szeder B, Bodor A, Schlosser G, Acs A, Turiak L, Buday L, Alexa A, Nyitray L, Remenyi A FEBS J. 2017 Oct 30. doi: 10.1111/febs.14311. PMID:29083550^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dalby KN, Morrice N, Caudwell FB, Avruch J, Cohen P. Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK. J Biol Chem. 1998 Jan 16;273(3):1496-505. PMID:9430688
↑ Shimamura A, Ballif BA, Richards SA, Blenis J. Rsk1 mediates a MEK-MAP kinase cell survival signal. Curr Biol. 2000 Feb 10;10(3):127-35. PMID:10679322
↑ Buck M, Poli V, Hunter T, Chojkier M. C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival. Mol Cell. 2001 Oct;8(4):807-16. PMID:11684016
↑ Wu J, Janknecht R. Regulation of the ETS transcription factor ER81 by the 90-kDa ribosomal S6 kinase 1 and protein kinase A. J Biol Chem. 2002 Nov 8;277(45):42669-79. Epub 2002 Sep 3. PMID:12213813 doi:10.1074/jbc.M205501200
↑ Hu Y, Fang X, Dunham SM, Prada C, Stachowiak EK, Stachowiak MK. 90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling. J Biol Chem. 2004 Jul 9;279(28):29325-35. Epub 2004 Apr 26. PMID:15117958 doi:10.1074/jbc.M311144200
↑ Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13489-94. Epub 2004 Sep 1. PMID:15342917 doi:10.1073/pnas.0405659101
↑ Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol. 2005 Oct 11;15(19):1762-7. PMID:16213824 doi:10.1016/j.cub.2005.08.050
↑ Wingate AD, Campbell DG, Peggie M, Arthur JS. Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation. Biochem J. 2006 Feb 1;393(Pt 3):715-24. PMID:16223362 doi:10.1042/BJ20050967
↑ Shahbazian D, Roux PP, Mieulet V, Cohen MS, Raught B, Taunton J, Hershey JW, Blenis J, Pende M, Sonenberg N. The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. EMBO J. 2006 Jun 21;25(12):2781-91. Epub 2006 Jun 8. PMID:16763566 doi:10.1038/sj.emboj.7601166
↑ Roux PP, Shahbazian D, Vu H, Holz MK, Cohen MS, Taunton J, Sonenberg N, Blenis J. RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation. J Biol Chem. 2007 May 11;282(19):14056-64. Epub 2007 Mar 14. PMID:17360704 doi:10.1074/jbc.M700906200
↑ Carriere A, Cargnello M, Julien LA, Gao H, Bonneil E, Thibault P, Roux PP. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biol. 2008 Sep 9;18(17):1269-77. doi: 10.1016/j.cub.2008.07.078. Epub 2008, Aug 21. PMID:18722121 doi:10.1016/j.cub.2008.07.078
↑ Gogl G, Biri-Kovacs B, Poti AL, Vadaszi H, Szeder B, Bodor A, Schlosser G, Acs A, Turiak L, Buday L, Alexa A, Nyitray L, Remenyi A. Dynamic control of RSK complexes by phosphoswitch-based regulation. FEBS J. 2017 Oct 30. doi: 10.1111/febs.14311. PMID:29083550 doi:http://dx.doi.org/10.1111/febs.14311

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/5n7g"

@@ Line 3: / Line 3: @@
 <StructureSection load='5n7g' size='340' side='right' caption='[[5n7g]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n7g]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N7G FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5n7g]] is a 3 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=5N7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N7G FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANXA2, ANX2, ANX2L4, CAL1H, LPC2D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=5n7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n7g OCA], [http://pdbe.org/5n7g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n7g RCSB], [http://www.ebi.ac.uk/pdbsum/5n7g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n7g ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Gogl, G]]

5n7g

From Proteopedia

Revision as of 08:10, 17 January 2018

MAGI-1 complexed with a synthetic pRSK1 peptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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