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2o26

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Structure of a class III RTK signaling assembly

Structural highlights

2o26 is a 8 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SCF_MOUSE Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.

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

Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. Three surface epitopes on SCF, an extended loop, the B and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon receptor binding. The SCF/KIT complex reveals a unique RTK dimerization assembly, and a novel recognition mode between four-helix bundle cytokines and Ig-family receptors. It serves as a framework for understanding the activation mechanisms of class III RTKs.

Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.,Liu H, Chen X, Focia PJ, He X EMBO J. 2007 Feb 7;26(3):891-901. Epub 2007 Jan 25. PMID:17255936^[1]

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

References

↑ Liu H, Chen X, Focia PJ, He X. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. EMBO J. 2007 Feb 7;26(3):891-901. Epub 2007 Jan 25. PMID:17255936

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2o26"

@@ Line 1: / Line 1: @@
 ==Structure of a class III RTK signaling assembly==
-<StructureSection load='2o26' size='340' side='right' caption='[[2o26]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='2o26' size='340' side='right'caption='[[2o26]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2o26]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O26 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2O26 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2o26]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O26 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene><br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o27|2o27]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kitlg, Kitl, Mgf, Sl, Slf ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Kit, Sl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=2o26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o26 OCA], [https://pdbe.org/2o26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o26 RCSB], [https://www.ebi.ac.uk/pdbsum/2o26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o26 ProSAT]</span></td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
+</table>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o26 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2o26 RCSB], [http://www.ebi.ac.uk/pdbsum/2o26 PDBsum]</span></td></tr>
-<table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/KIT_MOUSE KIT_MOUSE]] Note=Defects in Kit are the cause of the white-spotting phenotype (W). White-spotting variants induces severe effects on pigmentation, gametogenesis and hematopoiesis. Mice homozygous for W42 die perinatally of macrocytic anemia.<ref>PMID:1714377</ref> <ref>PMID:7509796</ref> <ref>PMID:9528781</ref> <ref>PMID:7527401</ref> <ref>PMID:17595334</ref> <ref>PMID:17255936</ref> <ref>PMID:1688471</ref> <ref>PMID:1693331</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/SCF_MOUSE SCF_MOUSE]] Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins. [[http://www.uniprot.org/uniprot/KIT_MOUSE KIT_MOUSE]] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.<ref>PMID:1698611</ref> <ref>PMID:1714377</ref> <ref>PMID:7509796</ref> <ref>PMID:9722617</ref> <ref>PMID:9528781</ref> <ref>PMID:18725415</ref> <ref>PMID:21037083</ref>
+[https://www.uniprot.org/uniprot/SCF_MOUSE SCF_MOUSE] Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o2/2o26_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o2/2o26_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2o26 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 31: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2o26" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Tyrosine kinase|Tyrosine kinase]]
+*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Receptor protein-tyrosine kinase]]
+[[Category: Chen X]]
-[[Category: Chen, X.]]
+[[Category: Focia PJ]]
-[[Category: Focia, P J.]]
+[[Category: He X]]
-[[Category: He, X.]]
+[[Category: Liu H]]
-[[Category: Liu, H.]]
-[[Category: 4-helix bundle]]
-[[Category: Class iii]]
-[[Category: Cytokine]]
-[[Category: Cytokine-signaling protein complex]]
-[[Category: Growth factor]]
-[[Category: Receptor tyrosine kinase]]
-[[Category: Receptor-ligand complex]]
-[[Category: Stem cell factor]]

2o26

From Proteopedia

Current revision

Structure of a class III RTK signaling assembly

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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