2lk4
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2lk4]] 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=2LK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LK4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[2lk4]] 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=2LK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LK4 FirstGlance]. <br> | ||
| - | </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=2lk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lk4 OCA], [https://pdbe.org/2lk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lk4 RCSB], [https://www.ebi.ac.uk/pdbsum/2lk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lk4 ProSAT]</span></td></tr> | + | </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=2lk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lk4 OCA], [https://pdbe.org/2lk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lk4 RCSB], [https://www.ebi.ac.uk/pdbsum/2lk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lk4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[https://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> | [https://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> | ||
| - | <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. | ||
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| - | 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> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2lk4" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Structural and mechanistic insights into the interaction between PAT Pyk2 and Paxillin LD motif
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