Volarević S, Niklinska B B, Burns C M, Yamada H, June C H, Dumont F J, Ashwell J D
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1992 Sep 1;176(3):835-44. doi: 10.1084/jem.176.3.835.
CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen receptor (TCR)-mediated activation. In T cell variants expressing progressively lower levels of CD45 (from normal to undetectable), CD45 expression was inversely related to spontaneous tyrosine phosphorylation of multiple proteins, including the TCR zeta chain, and was directly correlated with TCR-driven phosphoinositide hydrolysis. The Ca2+ response in these cells was altered in an unexpected fashion. Unlike wild-type cells, stimulated CD45- cell populations did not manifest an early increase in intracellular Ca2+, but did exhibit a delayed and gradual increase in mean intracellular Ca2+. Computer-aided fluorescence imaging of individual cells revealed that CD45- cells experienced late Ca2+ oscillations that were not blocked by removal of extracellular Ca2+. CD45 revertants had the signaling properties of wild-type cells. Thus, CD45 has a profound influence on both TCR-mediated signaling and phosphotyrosine homeostasis, and its loss reveals a novel role for this tyrosine phosphatase in Ca2+ regulation.
CD45是一种跨膜酪氨酸磷酸酶,与T细胞抗原受体(TCR)介导的激活有关。在表达逐渐降低水平CD45(从正常到无法检测)的T细胞变体中,CD45表达与多种蛋白质(包括TCR ζ链)的自发酪氨酸磷酸化呈负相关,并且与TCR驱动的磷酸肌醇水解直接相关。这些细胞中的Ca2+反应以一种意想不到的方式发生改变。与野生型细胞不同,受刺激的CD45-细胞群体并未表现出细胞内Ca2+的早期增加,但确实表现出平均细胞内Ca2+的延迟和逐渐增加。对单个细胞的计算机辅助荧光成像显示,CD45-细胞经历了晚期Ca2+振荡,这种振荡不会因去除细胞外Ca2+而被阻断。CD45回复株具有野生型细胞的信号特性。因此,CD45对TCR介导的信号传导和磷酸酪氨酸稳态都有深远影响,其缺失揭示了这种酪氨酸磷酸酶在Ca2+调节中的新作用。