Regulation of AP-1 by MAPK Signaling in Metal-Stressed Sea Anemone

Maayan Agron, Vera Brekhman, David Morgenstern, Tamar Lotan

Research output: Contribution to journalArticlepeer-review


Background/Aims: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. Methods: Metal-stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation. Results: We show that in cnidarian, AP-1 is regulated differently than in bilaterian models. ERK2 and ERK5, the main MAPK drivers of AP-1 activation in Bilateria, down-regulated fos1 and jun1 transcription in anemones exposed to metal stress, whereas p38 MAPK, triggered transcription of jun1 but not fos1. Furthermore, our results reveal that GSK3-β is the main driver of the immediate stress response in Nematostella. GSK3-β triggered transcription of AP-1 and two other stress-related genes, egr1 and hsp70. Finally, phylogenetic analysis and protein characterization show that while MAPKs and GSK3-β are evolutionarily conserved, Fos and Jun proteins in Nematostella and other cnidarians lack important regulatory and phosphorylation sites found in Bilateria. Conclusion: These findings reveal alternative network interactions of conserved signaling kinases, providing insight into the evolutionary plasticity of immediate stress response mechanisms.

Original languageEnglish
Pages (from-to)952-964
Number of pages13
JournalCellular Physiology and Biochemistry
Issue number3
StatePublished - 27 Jun 2017

Bibliographical note

Funding Information:
We thank the Bioinformatics Service Unit at University of Haifa for their assistance with the phylogenetic analysis. The work was supported by the Israeli Ministry of Science and Technology (MOST). The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication

Publisher Copyright:
© 2017 The Author(s). Published by S. Karger AG, Basel.


  • AP-1
  • Cnidaria
  • Evolution
  • GSK3-β
  • MAPK
  • Nematostella vectensis
  • Stress

ASJC Scopus subject areas

  • Physiology


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