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| <StructureSection load='3lok' size='340' side='right'caption='[[3lok]], [[Resolution|resolution]] 2.48Å' scene=''> | | <StructureSection load='3lok' size='340' side='right'caption='[[3lok]], [[Resolution|resolution]] 2.48Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[3lok]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LOK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lok]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LOK FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DJK:N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE'>DJK</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.48Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2hwp|2hwp]], [[2qlq|2qlq]], [[2qq7|2qq7]], [[2qi8|2qi8]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DJK:N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE'>DJK</scene></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRC, v-Src sarcoma viral oncogene ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr> | + | |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></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=3lok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lok OCA], [https://pdbe.org/3lok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lok RCSB], [https://www.ebi.ac.uk/pdbsum/3lok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lok ProSAT]</span></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=3lok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lok OCA], [https://pdbe.org/3lok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lok RCSB], [https://www.ebi.ac.uk/pdbsum/3lok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lok ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
| + | [https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Chick]] | + | [[Category: Gallus gallus]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Non-specific protein-tyrosine kinase]]
| + | [[Category: Gruetter C]] |
- | [[Category: Gruetter, C]] | + | [[Category: Rauh D]] |
- | [[Category: Rauh, D]] | + | [[Category: Rode HB]] |
- | [[Category: Rode, H B]] | + | |
- | [[Category: Atp-binding]]
| + | |
- | [[Category: Covalent inhibitor]]
| + | |
- | [[Category: Drug resistance]]
| + | |
- | [[Category: Irreversible inhibitor]]
| + | |
- | [[Category: Kinase]]
| + | |
- | [[Category: Lipoprotein]]
| + | |
- | [[Category: Myristate]]
| + | |
- | [[Category: Nucleotide-binding]]
| + | |
- | [[Category: Pd168393]]
| + | |
- | [[Category: Phosphoprotein]]
| + | |
- | [[Category: Proto-oncogene]]
| + | |
- | [[Category: Sh2 domain]]
| + | |
- | [[Category: Sh3 domain]]
| + | |
- | [[Category: Src kinase domain]]
| + | |
- | [[Category: Transferase-transferase inhibitor complex]]
| + | |
- | [[Category: Tyrosine-protein kinase]]
| + | |
| Structural highlights
Function
SRC_CHICK Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.[1] [2]
Publication Abstract from PubMed
Targeting protein kinases in cancer therapy with irreversible small-molecule inhibitors is moving to the forefront of kinase-inhibitor research and is thought to be an effective means of overcoming mutation-associated drug resistance in epidermal growth factor receptor kinase (EGFR). We generated a detection technique that allows direct measurements of covalent bond formation without relying on kinase activity, thereby allowing the straightforward investigation of the influence of steric clashes on covalent inhibitors in different resistant kinase mutants. The obtained results are discussed together with structural biology and biochemical studies of catalytic activity in both wild-type and gatekeeper mutated kinase variants to draw conclusions about the impact of steric hindrance and increased catalytic activity in drug-resistant kinase variants.
Characterization of irreversible kinase inhibitors by directly detecting covalent bond formation: a tool for dissecting kinase drug resistance.,Kluter S, Simard JR, Rode HB, Grutter C, Pawar V, Raaijmakers HC, Barf TA, Rabiller M, van Otterlo WA, Rauh D Chembiochem. 2010 Dec 10;11(18):2557-66. PMID:21080395[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kremer NE, D'Arcangelo G, Thomas SM, DeMarco M, Brugge JS, Halegoua S. Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of src and ras actions. J Cell Biol. 1991 Nov;115(3):809-19. PMID:1717492
- ↑ Simonson MS, Wang Y, Herman WH. Nuclear signaling by endothelin-1 requires Src protein-tyrosine kinases. J Biol Chem. 1996 Jan 5;271(1):77-82. PMID:8550628
- ↑ Kluter S, Simard JR, Rode HB, Grutter C, Pawar V, Raaijmakers HC, Barf TA, Rabiller M, van Otterlo WA, Rauh D. Characterization of irreversible kinase inhibitors by directly detecting covalent bond formation: a tool for dissecting kinase drug resistance. Chembiochem. 2010 Dec 10;11(18):2557-66. PMID:21080395 doi:10.1002/cbic.201000352
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