Phosphatidylinositol 3-kinase activation is required to form the NKG2D immunological synapse

被引:39
作者
Giurisato, Emanuele
Cella, Marina
Takai, Toshiyuki
Kurosaki, Tomohiro
Feng, Yungfeng
Longmore, Gregory D.
Colonna, Marco
Shaw, Andrey S. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[2] Tohoku Univ, Dept Expt Immunol, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan
[3] RIKEN, Res Ctr Allergy & Immunol, Lab Lynphocyte Differentiat, Tsurumi Ku, Kanagawa 2300045, Japan
[4] Washington Univ, Dept Med, St Louis, MO 63110 USA
[5] Washington Univ, Dept Cell Biol, St Louis, MO 63110 USA
关键词
D O I
10.1128/MCB.01477-07
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The receptor NKG2D allows natural killer (NK) cells to detect virally infected, stressed, and tumor cells. In human cells, NKG2D signaling is mediated through the associated DAP10 adapter. Here we show that engagement of NKG2D by itself is sufficient to stimulate the formation of the NK immunological synapse (NKIS), with recruitment of NKG2D to the center synapse. Mutagenesis studies of DAP10 revealed that the phosphatidylinositol 3-kinase binding site, but not the Grb2 binding site, was required and sufficient for recruitment of DAP10 to the NKIS. Surprisingly, we found that in the absence of the Grb2 binding site, Grb2 was still recruited to the NKIS. Since the recruitment of Grb2 was dependent on phosphatidylinositol-(3,4,5)-trisphosphate WIN, we explored the possibility that recruitment to the NKIS is mediated by a pleckstrin homology (PH) domain-containing binding partner for Grb2. We found that the PH domain of SOS1, but not that of Vav1, was able to be recruited by PIP3. These results provide new insights into the mechanism of immunological synapse formation and also demonstrate how multiple mechanisms can be used to recruit the same signaling proteins to the plasma membrane.
引用
收藏
页码:8583 / 8599
页数:17
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