Vivier E, da Silva A J, Ackerly M, Levine H, Rudd C E, Anderson P
Department of Pathology, Harvard Medical School, Boston, MA.
Eur J Immunol. 1993 Aug;23(8):1872-6. doi: 10.1002/eji.1830230821.
The CD16: zeta: gamma receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fc gamma domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of zeta and gamma are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the zeta subunit and the phospholipase C gamma-1 and gamma-2 isoforms. Here we show that CD16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16: zeta: gamma receptor complex, results in the tyrosine phosphorylation of a 70 kDa zeta-associated protein (pp70). Similarly, a 70-kDa zeta-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa zeta-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16: zeta: gamma complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.
CD16:ζ:γ受体复合物使自然杀伤（NK）细胞能够识别并清除被抗体包被的靶细胞。CD16的胞外结构域是免疫球蛋白Fcγ结构域的受体，而由ζ和γ组成的二硫键连接的同型和异型二聚体是该复合物细胞表面表达和信号转导特性所必需的。CD16的激活会启动酪氨酸激酶途径，该途径会诱导包括ζ亚基、磷脂酶Cγ-1和γ-2亚型在内的几种底物发生酪氨酸磷酸化。在此我们表明，对表达CD16:ζ:γ受体复合物的外周血NK细胞、白血病NK细胞或Jurkat转化细胞进行CD16刺激，会导致一种70 kDa的ζ相关蛋白（pp70）发生酪氨酸磷酸化。同样，T细胞中一种70 kDa的ζ相关磷蛋白已被证明是一种酪氨酸激酶（ZAP-70）。肽图谱分析表明，来自T细胞和NK细胞的70 kDa的ζ相关磷蛋白在结构上无法区分。我们得出结论，在导致NK细胞激活的CD16信号级联反应中，CD16:ζ:γ复合物可能利用了一种与ZAP-70相关的非受体酪氨酸激酶。
