Leitenberg D, Boutin Y, Lu D D, Bottomly K
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Immunity. 1999 Jun;10(6):701-11. doi: 10.1016/s1074-7613(00)80069-2.
CD45 is the predominant transmembrane tyrosine phosphatase in lymphocytes and is required for the efficient induction of T cell receptor signaling and activation. However, the regulation of CD45 activity and substrate specificity are poorly understood. In the present study, we demonstrate a basal biochemical association of CD45 with the T cell receptor complex that is regulated in part by CD45 isoform expression. Further, maintenance of CD45/TCR association is differentially regulated following TCR ligation with peptide: a partial agonist peptide induces CD45/TCR dissociation while an agonist peptide promotes sustained association in a CD4-dependent manner. These data suggest that T cell receptor signaling pathways may be modulated by altering access of CD45 to TCR-associated substrates involved in T cell activation.
CD45是淋巴细胞中主要的跨膜酪氨酸磷酸酶，是有效诱导T细胞受体信号传导和激活所必需的。然而，对CD45活性和底物特异性的调节了解甚少。在本研究中，我们证明了CD45与T细胞受体复合物之间存在基础生化关联，这种关联部分受CD45异构体表达的调节。此外，用肽连接TCR后，CD45/TCR关联的维持受到不同调节：部分激动剂肽诱导CD45/TCR解离，而激动剂肽以CD4依赖的方式促进持续关联。这些数据表明，T细胞受体信号通路可能通过改变CD45与参与T细胞激活的TCR相关底物的接触来调节。
