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Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk
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Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk
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Journal Article
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk
2009
Overview
The C-type lectin dectin-1 activates the transcription factor NF-kappaB through a Syk kinase-dependent signaling pathway to induce antifungal immunity. Here we show that dectin-1 expressed on human dendritic cells activates not only the Syk-dependent canonical NF-kappaB subunits p65 and c-Rel, but also the noncanonical NF-kappaB subunit RelB. Dectin-1, when stimulated by the beta-glucan curdlan or by Candida albicans, induced a second signaling pathway mediated by the serine-threonine kinase Raf-1, which integrated with the Syk pathway at the point of NF-kappaB activation. Raf-1 antagonized Syk-induced RelB activation by promoting sequestration of RelB into inactive p65-RelB dimers, thereby altering T helper cell differentiation. Thus, dectin-1 activates two independent signaling pathways, one through Syk and one through Raf-1, to induce immune responses.
Subject
/ Candida albicans - immunology
/ Cell Differentiation - immunology
/ Enzyme Activation - immunology
/ Enzyme-Linked Immunosorbent Assay
/ Gene Expression Regulation - immunology
/ Humans
/ Intracellular Signaling Peptides and Proteins - immunology
/ Intracellular Signaling Peptides and Proteins - metabolism
/ Membrane Proteins - immunology
/ Membrane Proteins - metabolism
/ Nerve Tissue Proteins - immunology
/ Nerve Tissue Proteins - metabolism
/ Protein-Tyrosine Kinases - immunology
/ Protein-Tyrosine Kinases - metabolism
/ Proto-Oncogene Proteins c-raf - immunology
/ Proto-Oncogene Proteins c-raf - metabolism
/ Reverse Transcriptase Polymerase Chain Reaction
/ Signal Transduction - immunology
/ T-Lymphocytes, Helper-Inducer - cytology
