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Originally published In Press as doi:10.1074/mcp.M800139-MCP200 on August 12, 2008.
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Molecular & Cellular Proteomics 8:32-44, 2009.
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.


Research

Quantitative Proteomics Reveals GIMAP Family Proteins 1 and 4 to Be Differentially Regulated during Human T Helper Cell Differentiation *,S

Jan-Jonas Filén{ddagger},§, Sanna Filén{ddagger},||, Robert Moulder{ddagger}, Soile Tuomela{ddagger},**, Helena Ahlfors{ddagger},§, Anne West{ddagger}, Petri Kouvonen{ddagger}, Suvi Kantola{ddagger}, Mari Björkman{ddagger}, Mikko Katajamaa{ddagger},§, Omid Rasool{ddagger}, Tuula A. Nyman{ddagger}{ddagger} and Riitta Lahesmaa{ddagger},§§

From the {ddagger} Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistökatu 6B, FI-20520 Turku, Finland, § The National Graduate School in Informational and Structural Biology, FI-20520 Turku, Finland, || The Drug Discovery Graduate School, FI-20520 Turku, Finland, ** Turku Graduate School of Biomedical Sciences, FI-20520 Turku, Finland, and {ddagger}{ddagger} Institute of Biotechnology, University of Helsinki, FI-00790 Helsinki, Finland

T helper (Th) cells differentiate into functionally distinct effector cell subsets of which Th1 and Th2 cells are best characterized. Besides T cell receptor signaling, IL-12-induced STAT4 and T-bet- and IL-4-induced STAT6 and GATA3 signaling pathways are the major players regulating the Th1 and Th2 differentiation process, respectively. However, there are likely to be other yet unknown factors or pathways involved. In this study we used quantitative proteomics exploiting cleavable ICAT labeling and LC-MS/MS to identify IL-4-regulated proteins from the microsomal fractions of CD4+ cells extracted from umbilical cord blood. We were able to identify 557 proteins of which 304 were also quantified. This study resulted in the identification of the down-regulation of small GTPases GIMAP1 and GIMAP4 by IL-4 during Th2 differentiation. We also showed that both GIMAP1 and GIMAP4 genes are up-regulated by IL-12 and other Th1 differentiation-inducing cytokines in cells induced to differentiate toward Th1 lineage and down-regulated by IL-4 in cells induced to Th2. Our results indicate that the GIMAP (GTPase of the immunity-associated protein) family of proteins is differentially regulated during Th cell differentiation.


§§ To whom correspondence should be addressed: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, P. O. Box 123, FIN-20521 Turku, Finland. Tel.: 358-2-333-8004; Fax: 358-2-333-8000; E-mail: riitta.lahesmaa{at}btk.fi


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