The mitogen-activated protein kinase (MAPK) pathways are signal transduction mechanisms that regulate many cellular processes in eukaryotic organisms, from yeasts to mammals. Multiple MAPKs regulate eukaryotic gene expression in response to various extracellular stimuli through phosphorylation of transcription factors. We have been studying the
Pmk
1 MAPK, a homologue of the mammalian ERK/MAPK in fission yeast. The
Pmk
1 MAPK regulates cell integrity and cell morphology. We have previously demonstrated that Atf1, a transcription factor downstream of the stress-activated MAPK pathway, serves also as a target of the
Pmk
1 MAPK signaling in fission yeast. Here, we identified
ecm33+ gene, encoding a glycosyl-phosphatidylinositol (GPI)-anchored cell surface protein as a transcriptional target of
Pmk
1 and Atf1. The gene expression of
ecm33+ is regulated by two transcription factors Atf1 and Mbx1. We also developed an
in vivo real-time monitoring system of Atf1 or Mbx1 transcriptional activity, which enables to monitor the activation of the
Pmk
1 MAPK pathway by various stimuli. Finally, we demonstrated that Ecm33 is involved in the negative regulation of the
Pmk
1 MAPK signaling through the control of Ca
2+ homeostasis. The
ecm33 deleted cells displayed Ca
2+ sensitivity and increased phosphorylation levels of
Pmk
1 MAPK. In addition, the Ecm33 overproducing cells displayed phenotypes closely similar to those of the
pmk1
knockout cell. Collectively, Ecm33 plays a role in the negative feedback regulation of Pmk
1 cell integrity signaling.
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