SHP1 Protein-tyrosine Phosphatase Inhibits gp91PHOX and p67 PHOX Expression by Inhibiting Interaction of PU.1, IRF1, Interferon Consensus Sequence-binding Protein, and CREB-binding Protein with Homologous Cis Elements in the CYBB and NCF2 Genes

Bryan Kautz, Renu Kakar, Ebenezer David, Elizabeth A. Eklund*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The CYBB and NCF2 genes encode the phagocyte respiratory burst oxidase proteins, gp91PHOX and p67PHOX. Previously, we identified homologous CYBB and NCF2 cis elements that are necessary for lineage-specific transcription during late myeloid differentiation. We determined that these homologous cis elements are activated by PU.1, IRF1, interferon consensus sequence-binding protein (ICSBP), and the CREB-binding protein (CBP). Since expression of PU.1 and ICSBP is lineage-restricted, our investigations identified a mechanism of lineage-specific CYBB and NCF2 transcription. Since PU.1, IRF1, ICSBP, and CBP are expressed in undifferentiated myeloid cells, our investigations did not determine the mechanism of differentiation stage-specific CYBB and NCF2 transcription. In the current investigations, we determine that SHP1 protein-tyrosine phosphatase (SHPI-PTP) inhibits gp91 PHOX and p67PHOX expression, in undifferentiated myeloid cell lines, by decreasing interaction of PU.1, IRF1, ICSBP, and CBP with the CYBB and NCF2 genes. We also determine that IRF1 and ICSBP are tyrosine-phosphorylated during interferon γ differentiation of myeloid cell lines, and we identify IRF1 and ICSBP tyrosine residues that are necessary for CYBB and NCF2 transcription. Therefore, these investigations identify a novel mechanism by which SHP1-PTP antagonizes myeloid differentiation and determine that tyrosine phosphorylation of IRF1 and ICSPB mediates stage-specific transcriptional activation in differentiating myeloid cells.

Original languageEnglish (US)
Pages (from-to)37868-37878
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number41
StatePublished - Oct 12 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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