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Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements.

Publication ,  Journal Article
Zhong, X-P; Maltzman, JS; Hainey, EA; Koretzky, GA
Published in: J Immunol
December 15, 2003

SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) is an adaptor molecule expressed in all hemopoietic cell lineages except mature B cells and is known to play critical roles in the function of T cells, mast cells, and platelets and in vascular differentiation. Although great progress has been achieved in our understanding of SLP-76 function, little is known about the mechanisms regulating its expression. In this study we report the initial characterization of essential elements that control SLP-76 transcription. We identify several DNase I-hypersensitive sites in the SLP-76 locus, with a prominent site located in its promoter region. This site exists in T cells and monocytic cells, but not in B cells or fibroblasts. Using transient transfection assays, we identify a 507-bp fragment containing the 5'-untranslated region of the first exon and the immediate upstream sequence that confers transcriptional activation in T cells and monocytic cells, but not in B cells. Analysis of the 5' ends of SLP-76 transcripts reveals differential regulation of SLP-76 transcription initiation between T cells and monocytic cells. Mutational and gel-shift analyses further indicate a critical role within this region for a binding site for Ets family transcription factors. The present study provides the first data to address the mechanisms controlling SLP-76 transcription by providing evidence for several key cis-regulatory elements in the promoter region.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 15, 2003

Volume

171

Issue

12

Start / End Page

6621 / 6629

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Transcription Initiation Site
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Antigen, T-Cell
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Phosphoproteins
 

Citation

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MLA
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Zhong, X.-P., Maltzman, J. S., Hainey, E. A., & Koretzky, G. A. (2003). Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements. J Immunol, 171(12), 6621–6629. https://doi.org/10.4049/jimmunol.171.12.6621
Zhong, Xiao-Ping, Jonathan S. Maltzman, Ehmonie A. Hainey, and Gary A. Koretzky. “Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements.J Immunol 171, no. 12 (December 15, 2003): 6621–29. https://doi.org/10.4049/jimmunol.171.12.6621.
Zhong, Xiao-Ping, et al. “Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements.J Immunol, vol. 171, no. 12, Dec. 2003, pp. 6621–29. Pubmed, doi:10.4049/jimmunol.171.12.6621.
Zhong X-P, Maltzman JS, Hainey EA, Koretzky GA. Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements. J Immunol. 2003 Dec 15;171(12):6621–6629.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 15, 2003

Volume

171

Issue

12

Start / End Page

6621 / 6629

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Transcription Initiation Site
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Antigen, T-Cell
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Phosphoproteins