Gratiot-Deans J, Keim D, Strahler J R, Turka L A, Hanash S
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109.
J Clin Invest. 1992 Oct;90(4):1576-81. doi: 10.1172/JCI116026.
Op18 (also termed prosolin/stathmin) is a highly conserved 18-kD cytosolic phosphoprotein expressed in low levels in mature resting G0 lymphocytes, but induced in late G1 and S phases after entry into the cell cycle. In addition to its induction in normal proliferating lymphocytes, Op18 has been found to occur at high levels in acute leukemias and in neuroendocrine tissue. The presence and rapid phosphorylation of Op18 after stimulation of proliferating cells correlates with subsequent functional responses of the cells, and, therefore, Op18 has been suggested to play a key role in signal transduction. The pattern of expression of Op18 during lymphoid development is of interest in view of its high levels of expression in acute leukemias, representing cells arrested at an immature stage, thus raising the possibility that Op18 may be regulated differently in mature and immature lymphoid cells. We report here that immature human thymocytes bearing the cortical double positive phenotype (CD4+CD8+) constitutively express high levels of Op18 protein. In contrast, in mature single positive thymocytes (CD3+CD4+ or CD3+CD8+), Op18 protein is expressed at a lower level, comparable to that seen in peripheral blood T cells. Cell cycle analysis demonstrated that most of the cells in the double positive thymocyte population expressing high levels of Op18 were noncycling and arrested in G0. Furthermore, there was no correlation between Op18 levels and the proportion of cycling cells in double positive thymocyte populations isolated from different thymuses. Interestingly, although Op18 protein levels did not increase any further after mitogenic stimulation of double positive thymocytes, an increase in Op18 phosphorylation was observed, thus coupling of Op18 phosphorylation to cell activation remained intact. Our results show that during lymphoid maturation Op18 expression is uncoupled from cell proliferation. These data also suggest that the ordered expression of proliferation-associated genes seen in mature T cells may be disrupted during T cell maturation.
Op18（也称为prosolin/Stathmin）是一种高度保守的18kD胞质磷蛋白，在成熟静止的G0淋巴细胞中低水平表达，但在进入细胞周期后的G1晚期和S期被诱导表达。除了在正常增殖淋巴细胞中被诱导表达外，Op18还在急性白血病和神经内分泌组织中高水平表达。增殖细胞受到刺激后Op18的存在及其快速磷酸化与细胞随后的功能反应相关，因此，有人提出Op18在信号转导中起关键作用。鉴于Op18在急性白血病（代表停滞在未成熟阶段的细胞）中高水平表达，其在淋巴细胞发育过程中的表达模式备受关注，这就增加了Op18在成熟和未成熟淋巴细胞中可能受到不同调节的可能性。我们在此报告，具有皮质双阳性表型（CD4+CD8+）的未成熟人类胸腺细胞组成性地高水平表达Op18蛋白。相比之下，在成熟的单阳性胸腺细胞（CD3+CD4+或CD3+CD8+）中，Op18蛋白的表达水平较低，与外周血T细胞中的水平相当。细胞周期分析表明，表达高水平Op18的双阳性胸腺细胞群体中的大多数细胞处于非循环状态并停滞在G0期。此外，从不同胸腺分离的双阳性胸腺细胞群体中，Op18水平与循环细胞比例之间没有相关性。有趣的是，尽管双阳性胸腺细胞在有丝分裂原刺激后Op18蛋白水平没有进一步增加，但观察到Op18磷酸化增加，因此Op18磷酸化与细胞激活的偶联仍然完整。我们的结果表明，在淋巴细胞成熟过程中，Op18的表达与细胞增殖解偶联。这些数据还表明，成熟T细胞中所见的增殖相关基因的有序表达在T细胞成熟过程中可能会被破坏。
