Source:http://linkedlifedata.com/resource/pubmed/id/21220694
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-2-3
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pubmed:abstractText |
GM-CSF is an important cytokine involved in myeloid differentiation and inflammatory processes. Signaling through the GM-CSFR also plays a critical role in the generation of monocyte-derived dendritic cells (DC). In this article, we report that the Src-like adaptor protein (SLAP) functions as a negative regulator of the GM-CSFR. In bone marrow-derived DC (BM-DC) lacking SLAP and the closely related SLAP2, downregulation of GM-CSFR? is impaired, leading to enhanced phosphorylation of Jak2 and prolonged activation of Akt and Erk1/2 in response to GM-CSF stimulation. Compared with wild-type bone marrow, SLAP/SLAP2(-/-) bone marrow gave rise to similar numbers of CD11c(+) and CD11b(+) DC, but SLAP/SLAP2(-/-) BM-DC failed to acquire high levels of MHC class II, CD80, and CD86, indicating an impairment in maturation. Furthermore, MHC class II expression in SLAP/SLAP2(-/-) BM-DC was rescued by decreasing GM-CSF concentration, suggesting that enhanced GM-CSF signaling mediates the block in maturation. In addition, SLAP/SLAP2(-/-) BM-DC produced less IL-12 and TNF-? in response to LPS compared with controls and failed to stimulate T cells in an MLR. Ag-specific T cell activation assays showed that SLAP/SLAP2(-/-) BM-DC were less robust at inducing IFN-? secretion by DO11.10 T cells. These results indicated that SLAP-mediated GM-CSFR regulation is important for the generation of functionally mature monocytic DC.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Csf2rb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokine Receptor Common beta...,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Sla protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sla2 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
186
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1923-33
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pubmed:meshHeading |
pubmed-meshheading:21220694-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21220694-Animals,
pubmed-meshheading:21220694-Cell Differentiation,
pubmed-meshheading:21220694-Cytokine Receptor Common beta Subunit,
pubmed-meshheading:21220694-Dendritic Cells,
pubmed-meshheading:21220694-Down-Regulation,
pubmed-meshheading:21220694-Growth Inhibitors,
pubmed-meshheading:21220694-Mice,
pubmed-meshheading:21220694-Mice, Knockout,
pubmed-meshheading:21220694-Mice, Transgenic,
pubmed-meshheading:21220694-Monocytes,
pubmed-meshheading:21220694-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:21220694-Signal Transduction
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pubmed:year |
2011
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pubmed:articleTitle |
The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation.
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pubmed:affiliation |
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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