Skip to main content

Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor.

Publication ,  Journal Article
Li, Q; Vaingankar, SM; Green, HM; Martins-Green, M
Published in: J Biol Chem
May 28, 1999

Using primary fibroblasts in culture, we have investigated the signal transduction mechanisms by which phorbol esters, a class of tumor promoters, activate the 9E3 gene and its chemokine product the chicken chemotactic and angiogenic factor. This gene is highly stimulated by phorbol 12,13-dibutyrate (PDBu) via three pathways: (i) a small contribution through protein kinase C (the commonly recognized pathway for these tumor promoters), (ii) a contribution involving tyrosine kinases, and (iii) a larger contribution via pathways that can be interrupted by dexamethasone. All three of these pathways converge into the mitogen-activated protein kinases, MEK1/ERK2. Using a luciferase reporter system, we show that although both the AP-1 and PDRIIkB (a NFkappaB-like factor in chickens) response elements are capable of activation in these normal cells, regions of the 9E3 promoter containing them are unresponsive to PDBu stimulation. In contrast, we show for the first time that activation by PDBu occurs through a segment of the promoter containing Elk1 response elements; deletion and mutation of these elements abrogates 9E3/chicken chemotactic and angiogenic factor expression. Electrophoretic mobility shift assays and functional studies using PathDetect systems show that stimulation of the cells by phorbol esters leads to activation of the Elk1 transcription factor, which binds to its element in the 9E3 promoter.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 28, 1999

Volume

274

Issue

22

Start / End Page

15454 / 15465

Location

United States

Related Subject Headings

  • ets-Domain Protein Elk-1
  • Transcription Factors
  • Transcription Factor AP-1
  • Signal Transduction
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Promoter Regions, Genetic
  • Potassium Channels
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, Q., Vaingankar, S. M., Green, H. M., & Martins-Green, M. (1999). Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor. J Biol Chem, 274(22), 15454–15465. https://doi.org/10.1074/jbc.274.22.15454
Li, Q., S. M. Vaingankar, H. M. Green, and M. Martins-Green. “Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor.J Biol Chem 274, no. 22 (May 28, 1999): 15454–65. https://doi.org/10.1074/jbc.274.22.15454.
Li, Q., et al. “Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor.J Biol Chem, vol. 274, no. 22, May 1999, pp. 15454–65. Pubmed, doi:10.1074/jbc.274.22.15454.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 28, 1999

Volume

274

Issue

22

Start / End Page

15454 / 15465

Location

United States

Related Subject Headings

  • ets-Domain Protein Elk-1
  • Transcription Factors
  • Transcription Factor AP-1
  • Signal Transduction
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Promoter Regions, Genetic
  • Potassium Channels