| Stage-specific requirement of a mitogen-activated protein kinase by Trypanosoma brucei. | |
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MedLine Citation:
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PMID: 12429824 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In cycling between the mammalian host and the tsetse fly vector, African trypanosomes undergo adaptive differentiation steps that are coupled to growth control. The signaling pathways underlying these cellular processes are largely unknown. Mitogen-activated protein kinases (MAPKs) are known mediators of growth and differentiation in other eukaryotic organisms. To establish the function of a MAPK homologue, TbMAPK2, in T. brucei, a null mutant was constructed. Bloodstream forms of a deltamapk2/deltamapk2 clone were able to grow normally and exhibited no detectable phenotype. When these cells were triggered to differentiate in vitro, however, they developed to the procyclic (fly midgut) form with delayed kinetics and subsequently underwent cell cycle arrest. Introduction of an ectopic copy of the TbMAPK2 gene into the null mutant restored its ability to differentiate and to divide. In contrast, a TbMAPK2 mutant, in which the T190 and Y192 residues of the activating phosphorylation site were replaced by A and F, was unable to restore the growth and differentiation phenotypes. Analysis of the DNA content and the nucleus/kinetoplast configuration of individual cells showed that the null mutant was arrested in all phases of the cell cycle and that 25-30% of the cells had failed to segregate their nucleus and kinetoplast correctly. This implies that cell cycle progression by the procyclic form depends on a constitutive stimulus exerted by the signaling cascade operating through TbMAPK2. |
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Authors:
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Ingrid B Müller; Debora Domenicali-Pfister; Isabel Roditi; Erik Vassella |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular biology of the cell Volume: 13 ISSN: 1059-1524 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-11-13 Completed Date: 2003-07-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 3787-99 Citation Subset: IM |
Affiliation:
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Institut für Zellbiologie, Universität Bern, CH-3012 Bern, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Cell Cycle / physiology Cell Differentiation / physiology Cell Division / physiology DNA / metabolism MAP Kinase Signaling System / physiology* Mitogen-Activated Protein Kinases / genetics, metabolism* Molecular Sequence Data Mutation Protozoan Proteins / genetics, metabolism* Sequence Alignment Trypanosoma brucei brucei / enzymology*, growth & development*, physiology |
| Chemical | |
Reg. No./Substance:
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0/Protozoan Proteins; 9007-49-2/DNA; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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