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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhong, X-P; Maltzman, JS; Hainey, EA; Koretzky, GA

Published Date

  • December 15, 2003

Published In

Volume / Issue

  • 171 / 12

Start / End Page

  • 6621 - 6629

PubMed ID

  • 14662865

Pubmed Central ID

  • 14662865

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.171.12.6621

Language

  • eng

Conference Location

  • United States