期刊
NATURE IMMUNOLOGY
卷 12, 期 11, 页码 1105-U114出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2120
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资金
- US National Institutes of Health [CA35299]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [23113521]
- United States-Israel Binational Science Foundation
- Grants-in-Aid for Scientific Research [21590548, 19109005, 19059013, 25113725] Funding Source: KAKEN
Protein kinase C-theta (PKC-theta) translocates to the center of the immunological synapse, but the underlying mechanism and its importance in T cell activation are unknown. Here we found that the V3 domain of PKC-theta was necessary and sufficient for localization to the immunological synapse mediated by association with the coreceptor CD28 and dependent on the kinase Lck. We identified a conserved proline-rich motif in V3 required for association with CD28 and immunological synapse localization. We found association with CD28 to be essential for PKC-theta-mediated downstream signaling and the differentiation of T helper type 2 cells (T(H)2 cells) and interleukin 17-producing helper T cells (T(H)17 cells) but not of T helper type 1 cells (T(H)1 cells). Ectopic expression of V3 sequestered PKC-theta from the immunological synapse and interfered with its functions. Our results identify a unique mode of CD28 signaling, establish a molecular basis for the immunological synapse localization of PKC-theta and indicate V3-based 'decoys' may be therapeutic modalities for T cell-mediated inflammatory diseases.
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