期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 15, 页码 6329-6334出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0611655104
关键词
costimulatory molecules; conjugation; cytoskeletal remodeling; immune synapse
资金
- NIAID NIH HHS [R01 AI050207, R56 AI053330, R01 AI053330, AI053330, AI050207] Funding Source: Medline
Natural killer (NK) cells are components of the innate immune system that recognize and kill tumor or virus-infected target cells through specific NK activating receptor/ligand interactions. Lymphocyte function-associated antigen (LFA)-1 and its ligand ICAM-1 are also required to initiate conjugation and actin cytoskeletal remodeling. The NK activating receptors, many of which are expressed on a single NK cell, signal the polarization of the microtubule organizing center (MTOC) together with cytolytic granules to the synapse with target cells. After ligation of any one of these receptors, Src family kinases initiate activation of two signal pathways, the phosphoinositide-3 kinase -> ERK2 and the phospholipase C gamma -> JNK1 pathways. Both are required for polarization of the MTOC and cytolytic granules, a prerequisite for killing the targets. Crosslinking of CD28, NKG2D, NKp30, NKp46, NKG2C/CD94, or 2B4 leads to the phosphorylation of both ERK2 and JNK1, although they use different proximal signaling modules. Thus, many, if not all, activating receptors stimulate these two distal pathways, independent of the proximal signaling module used. By contrast, CD2, DNAM-1, and beta(1)-integrin crosslinking do not activate either pathway; they may be costimulatory molecules or have another function in the synapse.
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