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Role of mitogen-activated protein kinase Sty1 in regulation of eukaryotic initiation factor 2alpha kinases in response to environmental stress in Schizosaccharomyces pombe.
Eukaryot Cell. 2010 Jan; 9(1):194-207.EC

Abstract

The mitogen-activated protein kinase (MAPK) Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. In fission yeast, three distinct eukaryotic initiation factor 2alpha (eIF2alpha) kinases, two mammalian HRI-related protein kinases (Hri1 and Hri2) and the Gcn2 ortholog, regulate protein synthesis in response to cellular stress conditions. In this study, we demonstrate that both Hri1 and Hri2 exhibited an autokinase activity, specifically phosphorylated eIF2alpha, and functionally replaced the endogenous Saccharomyces cerevisiae Gcn2. We further show that Gcn2, but not Hri1 or Hri2, is activated early after exposure to hydrogen peroxide and methyl methanesulfonate (MMS). Cells lacking Gcn2 exhibit a later activation of Hri2. The activated MAPK Sty1 negatively regulates Gcn2 and Hri2 activities under oxidative stress but not in response to MMS. In contrast, Hri2 is the primary activated eIF2alpha kinase in response to heat shock. In this case, the activation of Sty1 appears to be transitory and does not contribute to the modulation of the eIF2alpha kinase stress pathway. In strains lacking Hri2, a type 2A protein phosphatase is activated soon after heat shock to reduce eIF2alpha phosphorylation. Finally, the MAPK Sty1, but not the eIF2alpha kinases, is essential for survival upon oxidative stress or heat shock, but not upon MMS treatment. These findings point to a regulatory coordination between the Sty1 MAPK and eIF2alpha kinase pathways for a particular range of stress responses.

Authors+Show Affiliations

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19880757

Citation

Berlanga, Juan José, et al. "Role of Mitogen-activated Protein Kinase Sty1 in Regulation of Eukaryotic Initiation Factor 2alpha Kinases in Response to Environmental Stress in Schizosaccharomyces Pombe." Eukaryotic Cell, vol. 9, no. 1, 2010, pp. 194-207.
Berlanga JJ, Rivero D, Martín R, et al. Role of mitogen-activated protein kinase Sty1 in regulation of eukaryotic initiation factor 2alpha kinases in response to environmental stress in Schizosaccharomyces pombe. Eukaryot Cell. 2010;9(1):194-207.
Berlanga, J. J., Rivero, D., Martín, R., Herrero, S., Moreno, S., & de Haro, C. (2010). Role of mitogen-activated protein kinase Sty1 in regulation of eukaryotic initiation factor 2alpha kinases in response to environmental stress in Schizosaccharomyces pombe. Eukaryotic Cell, 9(1), 194-207. https://doi.org/10.1128/EC.00185-09
Berlanga JJ, et al. Role of Mitogen-activated Protein Kinase Sty1 in Regulation of Eukaryotic Initiation Factor 2alpha Kinases in Response to Environmental Stress in Schizosaccharomyces Pombe. Eukaryot Cell. 2010;9(1):194-207. PubMed PMID: 19880757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of mitogen-activated protein kinase Sty1 in regulation of eukaryotic initiation factor 2alpha kinases in response to environmental stress in Schizosaccharomyces pombe. AU - Berlanga,Juan José, AU - Rivero,Damariz, AU - Martín,Ruth, AU - Herrero,Saturnino, AU - Moreno,Sergio, AU - de Haro,César, Y1 - 2009/10/30/ PY - 2009/11/3/entrez PY - 2009/11/3/pubmed PY - 2010/4/17/medline SP - 194 EP - 207 JF - Eukaryotic cell JO - Eukaryot Cell VL - 9 IS - 1 N2 - The mitogen-activated protein kinase (MAPK) Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. In fission yeast, three distinct eukaryotic initiation factor 2alpha (eIF2alpha) kinases, two mammalian HRI-related protein kinases (Hri1 and Hri2) and the Gcn2 ortholog, regulate protein synthesis in response to cellular stress conditions. In this study, we demonstrate that both Hri1 and Hri2 exhibited an autokinase activity, specifically phosphorylated eIF2alpha, and functionally replaced the endogenous Saccharomyces cerevisiae Gcn2. We further show that Gcn2, but not Hri1 or Hri2, is activated early after exposure to hydrogen peroxide and methyl methanesulfonate (MMS). Cells lacking Gcn2 exhibit a later activation of Hri2. The activated MAPK Sty1 negatively regulates Gcn2 and Hri2 activities under oxidative stress but not in response to MMS. In contrast, Hri2 is the primary activated eIF2alpha kinase in response to heat shock. In this case, the activation of Sty1 appears to be transitory and does not contribute to the modulation of the eIF2alpha kinase stress pathway. In strains lacking Hri2, a type 2A protein phosphatase is activated soon after heat shock to reduce eIF2alpha phosphorylation. Finally, the MAPK Sty1, but not the eIF2alpha kinases, is essential for survival upon oxidative stress or heat shock, but not upon MMS treatment. These findings point to a regulatory coordination between the Sty1 MAPK and eIF2alpha kinase pathways for a particular range of stress responses. SN - 1535-9786 UR - https://www.unboundmedicine.com/medline/citation/19880757/Role_of_mitogen_activated_protein_kinase_Sty1_in_regulation_of_eukaryotic_initiation_factor_2alpha_kinases_in_response_to_environmental_stress_in_Schizosaccharomyces_pombe_ L2 - https://journals.asm.org/doi/10.1128/EC.00185-09?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -