Desai D M, Sap J, Schlessinger J, Weiss A
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Cell. 1993 May 7;73(3):541-54. doi: 10.1016/0092-8674(93)90141-c.
CD45, a transmembrane protein tyrosine phosphatase (PTPase), is required for TCR signaling. Multiple CD45 isoforms, differing in the extracellular domain, are expressed in a tissue- and activation-specific manner, suggesting an important function for this domain. We report that a chimeric protein in which the extracellular and transmembrane domains of CD45 are replaced with those of the EGF receptor (EGFR) is able to restore TCR signaling in a CD45-deficient cell. Thus, the cytoplasmic domain of CD45 is necessary and sufficient for TCR signal transduction. Moreover, EGFR ligands functionally inactivate the EGFR-CD45 chimera in a manner that is dependent on dimerization of the chimeric protein. Inactivation of EGFR-CD45 chimera function results in the loss of TCR signaling, indicating that CD45 function is continuously required for TCR-mediated proximal signaling events. These results suggest that ligand-mediated regulation of receptor-PTPases may have mechanistic similarities with receptor tyrosine kinases.
CD45是一种跨膜蛋白酪氨酸磷酸酶（PTPase），是TCR信号传导所必需的。多种细胞外结构域不同的CD45异构体以组织和激活特异性的方式表达，表明该结构域具有重要功能。我们报道，一种嵌合蛋白，其中CD45的细胞外和跨膜结构域被表皮生长因子受体（EGFR）的相应结构域取代，能够在缺乏CD45的细胞中恢复TCR信号传导。因此，CD45的细胞质结构域对于TCR信号转导是必要且充分的。此外，EGFR配体以一种依赖于嵌合蛋白二聚化的方式在功能上使EGFR-CD45嵌合体失活。EGFR-CD45嵌合体功能的失活导致TCR信号传导丧失，表明TCR介导的近端信号事件持续需要CD45发挥功能。这些结果表明，配体介导的受体蛋白酪氨酸磷酸酶调节可能与受体酪氨酸激酶具有相似的机制。
