|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2011-2-25
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3) negatively regulated transforming growth factor-? (TGF-?)-mediated Th cell differentiation. Map3k2(-/-)Map3k3(Lck-Cre/-) mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2(-/-)Map3k3(Lck-Cre/-) naive CD4(+) T cells' differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-? stimulation in vitro. In addition, Map3k2(-/-)Map3k3(Lck-Cre/-) mice developed more severe experimental autoimmune encephalomyelitis. Map3k2(-/-)Map3k3(Lck-Cre/-) T cells exhibited impaired phosphorylation of SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-? responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-? signaling pathways is important in regulating Th cell differentiation.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1097-4180
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
25
|
|
pubmed:volume |
34
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
201-12
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:21333552-Animals,
pubmed-meshheading:21333552-Bone Marrow Transplantation,
pubmed-meshheading:21333552-Cell Differentiation,
pubmed-meshheading:21333552-Enzyme Activation,
pubmed-meshheading:21333552-Forkhead Transcription Factors,
pubmed-meshheading:21333552-Lymphocyte Count,
pubmed-meshheading:21333552-Lymphopenia,
pubmed-meshheading:21333552-MAP Kinase Kinase Kinase 2,
pubmed-meshheading:21333552-MAP Kinase Kinase Kinase 3,
pubmed-meshheading:21333552-MAP Kinase Signaling System,
pubmed-meshheading:21333552-Mice,
pubmed-meshheading:21333552-Mice, Inbred C57BL,
pubmed-meshheading:21333552-Mice, Knockout,
pubmed-meshheading:21333552-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:21333552-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:21333552-Phosphorylation,
pubmed-meshheading:21333552-Protein Processing, Post-Translational,
pubmed-meshheading:21333552-Protein Structure, Tertiary,
pubmed-meshheading:21333552-Receptors, Antigen, T-Cell,
pubmed-meshheading:21333552-Smad2 Protein,
pubmed-meshheading:21333552-Smad3 Protein,
pubmed-meshheading:21333552-Specific Pathogen-Free Organisms,
pubmed-meshheading:21333552-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:21333552-T-Lymphocytes, Regulatory,
pubmed-meshheading:21333552-Th17 Cells,
pubmed-meshheading:21333552-Transforming Growth Factor beta
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
The kinases MEKK2 and MEKK3 regulate transforming growth factor-?-mediated helper T cell differentiation.
|
|
pubmed:affiliation |
Department of Immunobiology and Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06519, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
