Quantitative proteomics reveals GIMAP family proteins 1 and 4 to be differentially regulated during human T helper cell differentiation.
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.
Filén
Jan-Jonas
JJ
Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Tykistökatu 6B, FI-20520 Turku, Finland.
Filén
Sanna
S
Moulder
Robert
R
Tuomela
Soile
S
Ahlfors
Helena
H
West
Anne
A
Kouvonen
Petri
P
Kantola
Suvi
S
Björkman
Mari
M
Katajamaa
Mikko
M
Rasool
Omid
O
Nyman
Tuula A
TA
Lahesmaa
Riitta
R
D017398:Alternative Splicing / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C450435:GIMAP1 protein, human; C485688:GIMAP4 protein, human; D016898:Interferon-alpha; D020382:Interleukin-18; D008565:Membrane Proteins; D020543:Proteome; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D019204:GTP-Binding Proteins