Mason L H, Willette-Brown J, Anderson S K, Gosselin P, Shores E W, Love P E, Ortaldo J R, McVicar D W
Laboratory of Experimental Immunology, Division of Basic Sciences, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
J Immunol. 1998 May 1;160(9):4148-52.
Ly-49D is an activating receptor on NK cells that does not become tyrosine phosphorylated upon activation. This report demonstrates that immunoprecipitation of Ly-49D, following pervanadate treatment or specific Ab cross-linking, coprecipitates a 16-kDa tyrosine-phosphorylated protein (pp16). Immunoblotting experiments and data from TCR-zeta/Fc epsilonRIgamma double knockout mice confirm that pp16 is not TCR-zeta, TCR-eta, or Fc epsilonRIgamma. Association of pp16 with Ly-49D involves a transmembrane arginine since mutation to leucine (Ly-49D[R54L]) abolishes association with pp16 in transfected P815 cells. In addition, Ly-49D(R54L) transfectants fail to mediate Ca2+ mobilization following Ab cross-linking. Therefore, signaling through Ly49D on NK cells depends on association with a distinct tyrosine phosphoprotein (pp16) in a manner analogous to that of TCR and FcR. Expression of this novel signaling peptide in both the NK and myeloid lineages indicates that pp16 is likely involved in the signal transduction cascade of additional receptor families.
Ly-49D是自然杀伤细胞（NK细胞）上的一种激活受体，激活后不会发生酪氨酸磷酸化。本报告表明，在过钒酸盐处理或特异性抗体交联后，对Ly-49D进行免疫沉淀，会共沉淀出一种16 kDa的酪氨酸磷酸化蛋白（pp16）。免疫印迹实验以及来自TCR-zeta/Fc epsilonRIgamma双敲除小鼠的数据证实，pp16不是TCR-zeta、TCR-eta或Fc epsilonRIgamma。pp16与Ly-49D的结合涉及一个跨膜精氨酸，因为突变为亮氨酸（Ly-49D[R54L]）会消除其在转染的P815细胞中与pp16的结合。此外，Ly-49D(R54L)转染细胞在抗体交联后无法介导Ca2+动员。因此，NK细胞上通过Ly49D的信号传导取决于与一种独特的酪氨酸磷蛋白（pp16）的结合，其方式类似于TCR和FcR。这种新型信号肽在NK和髓系细胞系中的表达表明，pp16可能参与了其他受体家族的信号转导级联反应。
