4r32: Difference between revisions

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-'''Unreleased structure'''
+==Crystal Structure Analysis of Pyk2 and Paxillin LD motifs==
+<StructureSection load='4r32' size='340' side='right' caption='[[4r32]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4r32]] is a 3 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3u3c 3u3c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R32 FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u3f|3u3f]]</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=4r32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r32 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r32 RCSB], [http://www.ebi.ac.uk/pdbsum/4r32 PDBsum]</span></td></tr>
+<table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/FAK2_HUMAN FAK2_HUMAN]] Note=Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.<ref>PMID:18339875</ref> <ref>PMID:18765415</ref> <ref>PMID:19648005</ref> <ref>PMID:21533080</ref> <ref>PMID:20001213</ref> <ref>PMID:19428251</ref> <ref>PMID:19244237</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/FAK2_HUMAN FAK2_HUMAN]] Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. 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 of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2.<ref>PMID:7544443</ref> <ref>PMID:8849729</ref> <ref>PMID:8670418</ref> <ref>PMID:10022920</ref> <ref>PMID:12771146</ref> <ref>PMID:12893833</ref> <ref>PMID:14585963</ref> <ref>PMID:15050747</ref> <ref>PMID:15166227</ref> <ref>PMID:17634955</ref> <ref>PMID:18339875</ref> <ref>PMID:18765415</ref> <ref>PMID:18086875</ref> <ref>PMID:18587400</ref> <ref>PMID:19207108</ref> <ref>PMID:19648005</ref> <ref>PMID:19086031</ref> <ref>PMID:20521079</ref> <ref>PMID:19880522</ref> <ref>PMID:20381867</ref> <ref>PMID:21357692</ref> <ref>PMID:21533080</ref> <ref>PMID:20001213</ref> <ref>PMID:19428251</ref> <ref>PMID:19244237</ref>  [[http://www.uniprot.org/uniprot/PAXI_CHICK PAXI_CHICK]] Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Binds in vitro to vinculin as well as to the SH3 domain of c-SRC and, when tyrosine phosphorylated, to the SH2 domain of v-CRK.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) subfamily of cytoplasmic tyrosine kinases. The C-terminal Pyk2 focal adhesion-targeting (Pyk2-FAT) domain binds to paxillin, an adhesion molecule. Paxillin has five leucine-aspartate (LD) motifs (LD1-LD5). Here, we show that the second LD motif of paxillin, LD2, interacts with Pyk2-FAT, similar to the known Pyk2-FAT/LD4 interaction. Both LD motifs can target two ligand-binding sites on Pyk2-FAT. Interestingly, they also share similar binding affinity for Pyk2-FAT with preferential association to one site relative to the other. Nevertheless, the LD2-LD4 region of paxillin (paxillin133-290) binds to Pyk2-FAT as a 1:1 complex. However, our data suggests that the Pyk2-FAT and paxillin complex is dynamic and it appears to be a mixture of two distinct conformations of paxillin which almost equally compete for Pyk2-FAT binding. These studies provide insight into the underlying selectivity of paxillin for Pyk2 and FAK which may influence the differing behavior of these two closely-related kinases in focal adhesion sites.
-The entry 4r32 is ON HOLD  until Paper Publication
+Structural and mechanistic insights into the interaction between Pyk2 and Paxillin LD motifs.,Vanarotti MS, Miller DJ, Guibao CD, Nourse A, Zheng JJ J Mol Biol. 2014 Aug 28. pii: S0022-2836(14)00457-4. doi:, 10.1016/j.jmb.2014.08.014. PMID:25174335<ref>PMID:25174335</ref>
-Authors: Vanarotti, M., Miller, D.J., Guibao, C.D., Nourse, A., Zheng, J.J.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal Structure Analysis of Pyk2 and Paxillin LD motifs
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Guibao, C D.]]
+[[Category: Miller, D J.]]
+[[Category: Nourse, A.]]
+[[Category: Vanarotti, M.]]
+[[Category: Zheng, J J.]]
+[[Category: 4-helix bundle]]
+[[Category: Cell adhesion]]
+[[Category: Focal adhesion]]
+[[Category: Paxillin]]
+[[Category: Tyrosine kinase]]