View source for 1jpa


==Crystal Structure of unphosphorylated EphB2 receptor tyrosine kinase and juxtamembrane region==
<StructureSection load='1jpa' size='340' side='right'caption='[[1jpa]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1jpa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JPA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=1jpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jpa OCA], [http://pdbe.org/1jpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jpa RCSB], [http://www.ebi.ac.uk/pdbsum/1jpa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jpa ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/EPHB2_MOUSE EPHB2_MOUSE]] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.<ref>PMID:8689685</ref> <ref>PMID:8947026</ref> <ref>PMID:9990854</ref> <ref>PMID:10839360</ref> <ref>PMID:14691139</ref> <ref>PMID:15223334</ref> <ref>PMID:21029865</ref>  
== 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/jp/1jpa_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/main_output.php?pdb_ID=1jpa ConSurf].
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== Publication Abstract from PubMed ==
The Eph receptor tyrosine kinase family is regulated by autophosphorylation within the juxtamembrane region and the kinase activation segment. We have solved the X-ray crystal structure to 1.9 A resolution of an autoinhibited, unphosphorylated form of EphB2 comprised of the juxtamembrane region and the kinase domain. The structure, supported by mutagenesis data, reveals that the juxtamembrane segment adopts a helical conformation that distorts the small lobe of the kinase domain, and blocks the activation segment from attaining an activated conformation. Phosphorylation of conserved juxtamembrane tyrosines would relieve this autoinhibition by disturbing the association of the juxtamembrane segment with the kinase domain, while liberating phosphotyrosine sites for binding SH2 domains of target proteins. We propose that the autoinhibitory mechanism employed by EphB2 is a more general device through which receptor tyrosine kinases are controlled.

Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region.,Wybenga-Groot LE, Baskin B, Ong SH, Tong J, Pawson T, Sicheri F Cell. 2001 Sep 21;106(6):745-57. PMID:11572780<ref>PMID:11572780</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1jpa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Pawson, T]]
[[Category: Sicheri, F]]
[[Category: Wybenga-Groot, L E]]
[[Category: Autoinhibited]]
[[Category: Juxtamembrane]]
[[Category: Receptor tyrosine kinase]]
[[Category: Transferase]]
[[Category: Unphosphorylated]]