Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C.
Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C.
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DOI：
10.1084/jem.184.1.295
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发表时间：
1996-07-01
期刊：
影响因子：
--
通讯作者：
Weiss A
中科院分区：
文献类型：
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作者：
Fry AM;Lanier LL;Weiss A
NKB 1是一个不断增长的杀伤细胞抑制受体（KIR）家族的成员。它在自然杀伤（NK）细胞和T细胞上表达，并且已经显示在与其配体HLA-B（Bw 4）相互作用后抑制这些细胞的细胞溶解功能。我们在这里证明，NKB 1的胞质区域能够抑制Jurkat细胞中的T细胞活化。NKB 1 KIR共有基序YxxL（x）26 YxxL的酪氨酸磷酸化诱导与蛋白酪氨酸磷酸酶1C（PTP 1C）的结合。重要的是，基序中两个酪氨酸的突变消除了NKB 1的抑制功能并消除了PTP 1C的结合。单个酪氨酸的突变分析表明，膜近端酪氨酸可能在介导抑制信号中起着至关重要的作用。这些结果表明，KIR不仅可以抑制细胞溶解活性，但也可以负调节T细胞受体激活事件，导致下游基因激活，并进一步支持一个模型，牵连PTP 1C作为介导的KIR抑制信号。
NKB1 is one member of a growing family of killer cell inhibitory receptors (KIR). It is expressed on natural killer (NK) cells and T cells, and has been shown to inhibit cytolytic functions of these cells upon interacting with its ligand, HLA-B (Bw4). We demonstrate here that the cytoplasmic region of NKB1 is capable of inhibiting T cell activation in Jurkat cells. The tyrosine phosphorylation of the NKB1 KIR consensus motif, YxxL(x)26 YxxL, induces an association with the protein tyrosine phosphatase 1C (PTP1C). Importantly, mutation of both tyrosines in the motif abolished the inhibitory functions of NKB1 and abrogated PTP1C association. Mutational analysis of the individual tyrosines suggest that the membrane proximal tyrosine may play a crucial role in mediating the inhibitory signal. These results demonstrate that KIR can not only inhibit cytolytic activity, but can also negatively regulate T cell receptor activation events that lead to downstream gene activation, and further supports a model that implicates PTP1C as a mediator in the KIR inhibitory signal.