Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase.
Diminished Ikaros function has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros is of paramount importance for normal lymphocyte ontogeny. Here we provide genetic and biochemical evidence...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3747153?pdf=render |
| _version_ | 1811296623598239744 |
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| author | Hong Ma Sanjive Qazi Zahide Ozer Jian Zhang Rita Ishkhanian Fatih M Uckun |
| author_facet | Hong Ma Sanjive Qazi Zahide Ozer Jian Zhang Rita Ishkhanian Fatih M Uckun |
| author_sort | Hong Ma |
| collection | DOAJ |
| description | Diminished Ikaros function has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros is of paramount importance for normal lymphocyte ontogeny. Here we provide genetic and biochemical evidence for a previously unknown function of Bruton's tyrosine kinase (BTK) as a partner and posttranslational regulator of Ikaros, a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis. We demonstrate that BTK phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. Our results further demonstrate that BTK-induced activating phosphorylation is critical for the optimal transcription factor function of Ikaros. |
| first_indexed | 2024-04-13T05:52:11Z |
| format | Article |
| id | doaj.art-607ba95772884b01bdd3ba20110abf62 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T05:52:11Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-607ba95772884b01bdd3ba20110abf622022-12-22T02:59:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7130210.1371/journal.pone.0071302Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase.Hong MaSanjive QaziZahide OzerJian ZhangRita IshkhanianFatih M UckunDiminished Ikaros function has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros is of paramount importance for normal lymphocyte ontogeny. Here we provide genetic and biochemical evidence for a previously unknown function of Bruton's tyrosine kinase (BTK) as a partner and posttranslational regulator of Ikaros, a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis. We demonstrate that BTK phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. Our results further demonstrate that BTK-induced activating phosphorylation is critical for the optimal transcription factor function of Ikaros.http://europepmc.org/articles/PMC3747153?pdf=render |
| spellingShingle | Hong Ma Sanjive Qazi Zahide Ozer Jian Zhang Rita Ishkhanian Fatih M Uckun Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. PLoS ONE |
| title | Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. |
| title_full | Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. |
| title_fullStr | Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. |
| title_full_unstemmed | Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. |
| title_short | Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. |
| title_sort | regulatory phosphorylation of ikaros by bruton s tyrosine kinase |
| url | http://europepmc.org/articles/PMC3747153?pdf=render |
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