The ubiquitous intracellular parasite Toxoplasma gondii (phylum Apicomplexa) differentiates into an encysted form (bradyzoite) that can repeatedly re-emerge as a life-threatening acute infection (tachyzoite) upon impairment of immunity. Since the switch from tachyzoite to bradyzoite is a stress-induced response, we sought to identify components related to the phosphorylation of the α subunit of eIF2 (eukaryotic initiation factor-2), a well-characterized event associated with stress remediation in other eukaryotic systems. In addition to characterizing Toxoplasma eIF2α (TgIF2α), we have discovered a novel eIF2 protein kinase, designated TgIF2K-A (Toxoplasma gondiiinitiation factor-2kinase). Although the catalytic domain of TgIF2K-A contains sequence and structural features that are conserved among members of the eIF2 kinase family, TgIF2K-A has an extended N-terminal region that is highly divergent from other eIF2 kinases. TgIF2K-A specifically phosphorylates the regulatory serine residue of yeast eIF2α in vitro and in vivo, and can modulate translation when expressed in the yeast model system. We also demonstrate that TgIF2K-A phosphorylates the analogous regulatory serine residue of recombinant TgIF2α in vitro. Finally, we demonstrate that TgIF2α phosphorylation in tachyzoites is enhanced in response to heat shock or alkaline stress, conditions known to induce parasite differentiation in vitro. Collectively, this study suggests that eIF2 kinase-mediated stress responses are conserved in Apicomplexa, and a novel family member exists that may control parasite-specific events, including the clinically relevant conversion into bradyzoite cysts.
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Research Article|
June 01 2004
Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control
William J. SULLIVAN, Jr;
William J. SULLIVAN, Jr
1
*Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, U.S.A.
1To whom correspondence should be addressed (e-mail wjsulliv@iupui.edu).
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Jana NARASIMHAN;
Jana NARASIMHAN
†Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, U.S.A.
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Micah M. BHATTI;
Micah M. BHATTI
*Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, U.S.A.
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Ronald C. WEK
Ronald C. WEK
†Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, U.S.A.
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Publisher: Portland Press Ltd
Received:
February 17 2004
Revision Received:
February 27 2004
Accepted:
March 01 2004
Accepted Manuscript online:
March 01 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 380 (2): 523–531.
Article history
Received:
February 17 2004
Revision Received:
February 27 2004
Accepted:
March 01 2004
Accepted Manuscript online:
March 01 2004
Citation
William J. SULLIVAN, Jana NARASIMHAN, Micah M. BHATTI, Ronald C. WEK; Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control. Biochem J 1 June 2004; 380 (2): 523–531. doi: https://doi.org/10.1042/bj20040262
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