The nonreceptor tyrosine kinase c-Abl phosphorylates Runx1 and regulates Runx1-mediated megakaryocyte maturation

The nonreceptor tyrosine kinase c-Abl phosphorylates Runx1 and regulates Runx1-mediated... The transcription factor Runx1 is an essential regulator of definitive hematopoiesis, megakaryocyte (MK) maturation, and lymphocyte differentiation. Runx1 mutations that interfere with its transcriptional activity are often present in leukemia patients. Recent work demonstrated that the transcriptional activity of Runx1 is regulated by kinase-mediated phosphorylation. In this study, we showed that c-Abl, but not Arg tyrosine kinase, associated with Runx1 both in cultured cells and in vitro. c-Abl-mediated tyrosine phosphorylation in the Runx1 transcription inhibition domain negatively regulated the transcriptional activity of Runx1 and inhibited Runx1-mediated MK maturation. Consistent with these findings, increased numbers of MKs were detected in the spleens and bone marrow of abl gene conditional knockout mice. Our findings demonstrate an important role of c-Abl kinase in Runx1-mediated MK maturation and platelet formation and provide a potential mechanism of Abl kinase-regulated hematopoiesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Elsevier

The nonreceptor tyrosine kinase c-Abl phosphorylates Runx1 and regulates Runx1-mediated megakaryocyte maturation

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
0167-4889
D.O.I.
10.1016/j.bbamcr.2018.05.001
Publisher site
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Abstract

The transcription factor Runx1 is an essential regulator of definitive hematopoiesis, megakaryocyte (MK) maturation, and lymphocyte differentiation. Runx1 mutations that interfere with its transcriptional activity are often present in leukemia patients. Recent work demonstrated that the transcriptional activity of Runx1 is regulated by kinase-mediated phosphorylation. In this study, we showed that c-Abl, but not Arg tyrosine kinase, associated with Runx1 both in cultured cells and in vitro. c-Abl-mediated tyrosine phosphorylation in the Runx1 transcription inhibition domain negatively regulated the transcriptional activity of Runx1 and inhibited Runx1-mediated MK maturation. Consistent with these findings, increased numbers of MKs were detected in the spleens and bone marrow of abl gene conditional knockout mice. Our findings demonstrate an important role of c-Abl kinase in Runx1-mediated MK maturation and platelet formation and provide a potential mechanism of Abl kinase-regulated hematopoiesis.

Journal

Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchElsevier

Published: Aug 1, 2018

References

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