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PLoS One. 2013 Aug 19;8(8):e71302. doi: 10.1371/journal.pone.0071302. eCollection 2013.

Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase.

Author information

1
Systems Immunobiology Laboratory, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California, United States of America.

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.

PMID:
23977012
PMCID:
PMC3747153
DOI:
10.1371/journal.pone.0071302
[Indexed for MEDLINE]
Free PMC Article

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