Defying c-Abl signaling circuits through small allosteric compounds
Many extracellular and intracellular signals promote the c-Abl tyrosine kinase activity. c-Abl in turn triggers a multitude of changes either in protein phosphorylation or in gene expression in the cell. Yet, c-Abl takes part in diverse signaling routes because of several domains linked to its catal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00392/full |
| _version_ | 1818827342032666624 |
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| author | Stefania eGonfloni |
| author_facet | Stefania eGonfloni |
| author_sort | Stefania eGonfloni |
| collection | DOAJ |
| description | Many extracellular and intracellular signals promote the c-Abl tyrosine kinase activity. c-Abl in turn triggers a multitude of changes either in protein phosphorylation or in gene expression in the cell. Yet, c-Abl takes part in diverse signaling routes because of several domains linked to its catalytic core. Complex conformational changes turn on and off its kinase activity. These changes affect surface features of the c-Abl kinase and likely its capability to bind actin and/or DNA. Two specific inhibitors (ATP-competitive or allosteric compounds) regulate the c-Abl kinase through different mechanisms. NMR studies show that a c-Abl fragment (SH3-SH2-linker-SH1) adopts different conformational states upon binding to each inhibitor. This supports an unconventional use for allosteric compounds to unraveling physiological c-Abl signaling circuits. |
| first_indexed | 2024-12-19T00:42:02Z |
| format | Article |
| id | doaj.art-65fc8a1d71c64a84a66725a4411760ea |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T00:42:02Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-65fc8a1d71c64a84a66725a4411760ea2022-12-21T20:44:27ZengFrontiers Media S.A.Frontiers in Genetics1664-80212014-11-01510.3389/fgene.2014.00392104478Defying c-Abl signaling circuits through small allosteric compoundsStefania eGonfloni0University of Rome Tor VergataMany extracellular and intracellular signals promote the c-Abl tyrosine kinase activity. c-Abl in turn triggers a multitude of changes either in protein phosphorylation or in gene expression in the cell. Yet, c-Abl takes part in diverse signaling routes because of several domains linked to its catalytic core. Complex conformational changes turn on and off its kinase activity. These changes affect surface features of the c-Abl kinase and likely its capability to bind actin and/or DNA. Two specific inhibitors (ATP-competitive or allosteric compounds) regulate the c-Abl kinase through different mechanisms. NMR studies show that a c-Abl fragment (SH3-SH2-linker-SH1) adopts different conformational states upon binding to each inhibitor. This supports an unconventional use for allosteric compounds to unraveling physiological c-Abl signaling circuits.http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00392/fullActin CytoskeletonStress responsesallosteric modulatorNeuronal degenerationc-Abl signaling motifs |
| spellingShingle | Stefania eGonfloni Defying c-Abl signaling circuits through small allosteric compounds Frontiers in Genetics Actin Cytoskeleton Stress responses allosteric modulator Neuronal degeneration c-Abl signaling motifs |
| title | Defying c-Abl signaling circuits through small allosteric compounds |
| title_full | Defying c-Abl signaling circuits through small allosteric compounds |
| title_fullStr | Defying c-Abl signaling circuits through small allosteric compounds |
| title_full_unstemmed | Defying c-Abl signaling circuits through small allosteric compounds |
| title_short | Defying c-Abl signaling circuits through small allosteric compounds |
| title_sort | defying c abl signaling circuits through small allosteric compounds |
| topic | Actin Cytoskeleton Stress responses allosteric modulator Neuronal degeneration c-Abl signaling motifs |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00392/full |
| work_keys_str_mv | AT stefaniaegonfloni defyingcablsignalingcircuitsthroughsmallallostericcompounds |