Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23977012.
- Also identified by DOI 10.1371/journal.pone.0071302 and PMC identifier 3747153.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- B-Lymphocytes
- Gene Expression Regulation, Leukemic
- Ikaros Transcription Factor
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
- Protein-Tyrosine Kinases