MAPK-mediated phosphorylation of GATA-1 promotes Bcl-XL expression and cell survival

Yung Luen Yu, Yun Jung Chiang, Yu Chun Chen, Michael Papetti, Chiun Gung Juo, Arthur I. Skoultchi, Jeffrey J.Y. Yen

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

In the interleukin 3-dependent hematopoietic cell line Ba/F3, inhibition of mitogen-activated protein kinase, a member of the MAPK/c-Jun N-terminal kinase/stress-activated protein kinase kinase family that plays an important role in cell growth and death control, rapidly leads to severe apoptosis. However, most of the antiapoptotic substrates of MAPK remain to be identified. Here we report that, upon interleukin-3 stimulation of Ba/F3 cells, the transcription factor GATA-1 is strongly phosphorylated at residue serine 26 by a MAPK-dependent pathway. Phosphorylation of GATA-1 increases GATA-1-mediated transcription of the E4bp4 survival gene without significantly changing the DNA-binding affinity of GATA-1. Further characterization of GATA-1 phosphorylation site mutants revealed that the antiapoptotic function of GATA-1 is strongly dependent upon its phosphorylation at the Ser-26 position and is probably mediated through its up-regulation of Bcl-XL expression. Taken together, our data demonstrate that MAPK-dependent GATA-1 phosphorylation is important for its transactivation of the E4bp4 gene, Bcl-XL expression and cell survival. Therefore, GATA-1 may represent a novel MAPK substrate that plays an essential role in a cytokine-mediated antiapoptotic response.

Original languageEnglish (US)
Pages (from-to)29533-29542
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number33
DOIs
StatePublished - Aug 19 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yu, Y. L., Chiang, Y. J., Chen, Y. C., Papetti, M., Juo, C. G., Skoultchi, A. I., & Yen, J. J. Y. (2005). MAPK-mediated phosphorylation of GATA-1 promotes Bcl-XL expression and cell survival. Journal of Biological Chemistry, 280(33), 29533-29542. https://doi.org/10.1074/jbc.M506514200