2eyy: Difference between revisions

New page: left|200px<br /> <applet load="2eyy" size="450" color="white" frame="true" align="right" spinBox="true" caption="2eyy" /> '''CT10-Regulated Kinase isoform I'''<br /> =...
 
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'''CT10-Regulated Kinase isoform I'''<br />


==Overview==
==CT10-Regulated Kinase isoform I==
CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the, oncoprotein CRK that regulate transcription and cytoskeletal, reorganization for cell growth and motility by linking tyrosine kinases to, small G proteins. CRKI shows substantial transforming activity, whereas, the activity of CRKII is low, and phosphorylated CRKII has no biological, activity whatsoever. The molecular mechanisms underlying the distinct, biological activities of the CRK proteins remain elusive. We determined, the solution structures of CRKI, CRKII and phosphorylated CRKII by NMR and, identified the molecular mechanism that gives rise to their activities., Results from mutational analysis using rodent 3Y1 fibroblasts were, consistent with those from the structural studies. Together, these data, suggest that the linker region modulates the binding of CRKII to its, targets, thus regulating cell growth and motility.
<StructureSection load='2eyy' size='340' side='right'caption='[[2eyy]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2eyy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EYY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2eyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eyy OCA], [https://pdbe.org/2eyy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2eyy RCSB], [https://www.ebi.ac.uk/pdbsum/2eyy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2eyy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CRK_HUMAN CRK_HUMAN] The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.<ref>PMID:1630456</ref> <ref>PMID:11870224</ref> <ref>PMID:17515907</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/ey/2eyy_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=2eyy ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK that regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. CRKI shows substantial transforming activity, whereas the activity of CRKII is low, and phosphorylated CRKII has no biological activity whatsoever. The molecular mechanisms underlying the distinct biological activities of the CRK proteins remain elusive. We determined the solution structures of CRKI, CRKII and phosphorylated CRKII by NMR and identified the molecular mechanism that gives rise to their activities. Results from mutational analysis using rodent 3Y1 fibroblasts were consistent with those from the structural studies. Together, these data suggest that the linker region modulates the binding of CRKII to its targets, thus regulating cell growth and motility.


==About this Structure==
Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.,Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y, Ogura K, Tanaka S, Inagaki F Nat Struct Mol Biol. 2007 Jun;14(6):503-10. Epub 2007 May 21. PMID:17515907<ref>PMID:17515907</ref>
2EYY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2EYY OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK., Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y, Ogura K, Tanaka S, Inagaki F, Nat Struct Mol Biol. 2007 Jun;14(6):503-10. Epub 2007 May 21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17515907 17515907]
</div>
<div class="pdbe-citations 2eyy" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Adapter molecule crk 3D structures|Adapter molecule crk 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Inagaki, F.]]
[[Category: Inagaki F]]
[[Category: Kobashigawa, Y.]]
[[Category: Kobashigawa Y]]
[[Category: Tanaka, S.]]
[[Category: Tanaka S]]
[[Category: sh2]]
[[Category: sh3]]
 
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