Zhu Jing W, Brdicka Tomas, Katsumoto Tamiko R, Lin Joseph, Weiss Arthur
Departments of Medicine and of Microbiology and Immunology, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California-San Francisco, San Francisco, CA 94143, USA.
Immunity. 2008 Feb;28(2):183-96. doi: 10.1016/j.immuni.2007.11.024. Epub 2008 Jan 31.
The receptor-type protein tyrosine phosphatase (RPTP) CD148 is thought to have an inhibitory function in signaling and proliferation in nonhematopoietic cells. However, its role in the immune system has not been thoroughly studied. Our analysis of CD148 loss-of-function mice showed that CD148 has a positive regulatory function in B cells and macrophages, similar to the role of CD45 as a positive regulator of Src family kinases (SFKs). Analysis of CD148 and CD45 doubly deficient B cells and macrophages revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SFKs accompanied by substantial alterations in B and myeloid lineage development and defective immunoreceptor signaling. Because these findings suggest the C-terminal tyrosine of SFKs is a common substrate for both CD148 and CD45 phosphatases and imply a level of redundancy not previously appreciated, a reassessment of the function of CD45 in the B and myeloid lineages based on prior data from the CD45-deficient mouse is warranted.
受体型蛋白酪氨酸磷酸酶（RPTP）CD148被认为在非造血细胞的信号传导和增殖中具有抑制功能。然而，其在免疫系统中的作用尚未得到充分研究。我们对CD148功能缺失小鼠的分析表明，CD148在B细胞和巨噬细胞中具有正向调节功能，类似于CD45作为Src家族激酶（SFK）正向调节因子的作用。对CD148和CD45双缺陷B细胞和巨噬细胞的分析显示，SFK的C末端抑制性酪氨酸发生过度磷酸化，同时B细胞和髓系谱系发育出现实质性改变，免疫受体信号传导存在缺陷。由于这些发现表明SFK的C末端酪氨酸是CD148和CD45磷酸酶的共同底物，并暗示了一种此前未被认识到的冗余程度，因此有必要根据来自CD45缺陷小鼠的先前数据，重新评估CD45在B细胞和髓系谱系中的功能。
