Signal transduction and the Ets family of transcription factors

Oncogene. 2000 Dec 18;19(55):6503-13. doi: 10.1038/sj.onc.1204036.


Cellular responses to environmental stimuli are controlled by a series of signaling cascades that transduce extracellular signals from ligand-activated cell surface receptors to the nucleus. Although most pathways were initially thought to be linear, it has become apparent that there is a dynamic interplay between signaling pathways that result in the complex pattern of cell-type specific responses required for proliferation, differentiation and survival. One group of nuclear effectors of these signaling pathways are the Ets family of transcription factors, directing cytoplasmic signals to the control of gene expression. This family is defined by a highly conserved DNA binding domain that binds the core consensus sequence GGAA/T. Signaling pathways such as the MAP kinases, Erk1 and 2, p38 and JNK, the PI3 kinases and Ca2+-specific signals activated by growth factors or cellular stresses, converge on the Ets family of factors, controlling their activity, protein partnerships and specification of downstream target genes. Interestingly, Ets family members can act as both upstream and downstream effectors of signaling pathways. As downstream effectors their activities are directly controlled by specific phosphorylations, resulting in their ability to activate or repress specific target genes. As upstream effectors they are responsible for the spacial and temporal expression or numerous growth factor receptors. This review provides a brief survey of what is known to date about how this family of transcription factors is regulated by cellular signaling with a special focus on Ras responsive elements (RREs), the MAP kinases (Erks, p38 and JNK) and Ca2+-specific pathways and includes a description of the multiple roles of Ets family members in the lymphoid system. Finally, we will discuss other potential mechanisms and pathways involved in the regulation of this important family of transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling / genetics
  • Calcium Signaling / physiology
  • DNA-Binding Proteins*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Enhancer Elements, Genetic
  • Forecasting
  • Hematopoiesis / genetics
  • Humans
  • Ion Transport / genetics
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology
  • Models, Biological
  • Multigene Family*
  • Phosphorylation
  • Polyomavirus / genetics
  • Polyomavirus / physiology
  • Potassium Channels / physiology
  • Protein Kinases / physiology
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins*
  • Signal Transduction* / genetics
  • Signal Transduction* / physiology
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • ets-Domain Protein Elk-1
  • ras Proteins / physiology


  • DNA-Binding Proteins
  • ERF protein, human
  • ETS2 protein, human
  • Potassium Channels
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • proto-oncogene protein Spi-1
  • Protein Kinases
  • ras Proteins
  • Calcium