Tangye S G, Wu J, Aversa G, de Vries J E, Lanier L L, Phillips J H
Immunobiology Department, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
J Immunol. 1998 Oct 15;161(8):3803-7.
T cell activation represents a balance between positive and negative signals delivered via distinct cell surface molecules. Many cytoplasmic protein tyrosine phosphatases are involved in regulating cellular responses by antagonizing the action of protein tyrosine kinases. CD148 is a receptor-type protein tyrosine phosphatase expressed by all human mononuclear cells. We have investigated the effect of CD148 on TCR-mediated activation of human T cells. Overexpression of wild-type, but not a phosphatase-deficient, CD148 in Jurkat T cells inhibited TCR-mediated activation, evidenced by reduced expression of the early activation Ag CD69, inhibition of tyrosine phosphorylation of many intracellular proteins including the critical protein tyrosine kinase ZAP-70, and impairment of mitogen-activated protein kinase activation. Taken together, these results suggest that CD148 is an important phosphatase involved in negatively regulating the proximal signaling events during activation of Ag-specific T cells.
T细胞活化代表了通过不同细胞表面分子传递的正向和负向信号之间的平衡。许多细胞质蛋白酪氨酸磷酸酶通过拮抗蛋白酪氨酸激酶的作用参与调节细胞反应。CD148是一种由所有人单核细胞表达的受体型蛋白酪氨酸磷酸酶。我们研究了CD148对TCR介导的人T细胞活化的影响。在Jurkat T细胞中过表达野生型而非磷酸酶缺陷型的CD148可抑制TCR介导的活化，这表现为早期活化抗原CD69的表达降低、包括关键蛋白酪氨酸激酶ZAP-70在内的许多细胞内蛋白的酪氨酸磷酸化受到抑制以及丝裂原活化蛋白激酶活化受损。综上所述，这些结果表明CD148是一种重要的磷酸酶，参与负向调节抗原特异性T细胞活化过程中的近端信号事件。
