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{{STRUCTURE_2j0m|  PDB=2j0m  |  SCENE=  }}
==Crystal structure a two-chain complex between the FERM and kinase domains of focal adhesion kinase.==
===Crystal structure a two-chain complex between the FERM and kinase domains of focal adhesion kinase.===
<StructureSection load='2j0m' size='340' side='right' caption='[[2j0m]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
{{ABSTRACT_PUBMED_17574028}}
== Structural highlights ==
<table><tr><td colspan='2'>[[2j0m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J0M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J0M FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4ST:1,2,3,4-TETRAHYDROGEN-STAUROSPORINE'>4ST</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ktm|1ktm]], [[1pv3|1pv3]], [[1qvx|1qvx]], [[2aeh|2aeh]], [[2al6|2al6]], [[2j0j|2j0j]], [[2j0k|2j0k]], [[2j0l|2j0l]]</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
<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=2j0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j0m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j0m RCSB], [http://www.ebi.ac.uk/pdbsum/2j0m PDBsum]</span></td></tr>
<table>
== 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/j0/2j0m_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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK. The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.


==Function==
Structural basis for the autoinhibition of focal adhesion kinase.,Lietha D, Cai X, Ceccarelli DF, Li Y, Schaller MD, Eck MJ Cell. 2007 Jun 15;129(6):1177-87. PMID:17574028<ref>PMID:17574028</ref>
[[http://www.uniprot.org/uniprot/FAK1_CHICK FAK1_CHICK]] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development, embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), ephrin receptors, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Regulates P53/TP53 activity and stability. Phosphorylates SRC; this increases SRC kinase activity. Isoform 2 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling.<ref>PMID:15494733</ref> <ref>PMID:15494734</ref> <ref>PMID:15494732</ref> <ref>PMID:20705914</ref> <ref>PMID:21852560</ref> <ref>PMID:21937583</ref>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[2j0m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J0M OCA].
</div>


==See Also==
==See Also==
*[[Focal adhesion kinase|Focal adhesion kinase]]
*[[Focal adhesion kinase|Focal adhesion kinase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:017574028</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Chick]]
[[Category: Chick]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Non-specific protein-tyrosine kinase]]

Revision as of 13:25, 3 October 2014

Crystal structure a two-chain complex between the FERM and kinase domains of focal adhesion kinase.Crystal structure a two-chain complex between the FERM and kinase domains of focal adhesion kinase.

Structural highlights

2j0m is a 2 chain structure with sequence from Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:1ktm, 1pv3, 1qvx, 2aeh, 2al6, 2j0j, 2j0k, 2j0l
Activity:Non-specific protein-tyrosine kinase, with EC number 2.7.10.2
Resources:FirstGlance, OCA, RCSB, PDBsum

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

Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK. The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.

Structural basis for the autoinhibition of focal adhesion kinase.,Lietha D, Cai X, Ceccarelli DF, Li Y, Schaller MD, Eck MJ Cell. 2007 Jun 15;129(6):1177-87. PMID:17574028[1]

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

See Also

References

  1. ↑ Lietha D, Cai X, Ceccarelli DF, Li Y, Schaller MD, Eck MJ. Structural basis for the autoinhibition of focal adhesion kinase. Cell. 2007 Jun 15;129(6):1177-87. PMID:17574028 doi:10.1016/j.cell.2007.05.041

2j0m, resolution 2.80Å

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