The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
J Immunotoxicol. 2010 Mar;7(1):8-14. doi: 10.3109/15476910903427654.
PICOT was originally discovered as a protein kinase C (PKC) binding protein in human Jurkat T-lymphocytes in which it was found to modulate PKCtheta-dependent functions. In addition, RT-PCR analysis suggested the expression of PICOT in a wide range of organs and cell types, including cells that are devoid of PKCtheta. We aimed at analyzing the expression of the PICOT protein in mouse lymphoid organs, and to compare them with those of Jurkat T-lymphocytes and other cell lines. We also analyzed whether PICOT expression in T-lymphocytes is dependent on the presence of PKCtheta, and whether it correlates with cell growth rate. Western blot analyses demonstrated PICOT expression in all lymphoid organs and cell lines tested. In addition, similar expression levels were observed in lymphoid organs of wild-type and PKCtheta-null mice, suggesting that PICOT expression in T-lymphocytes is independent of PKCtheta. However, PICOT expression levels were higher in Jurkat T-lymphocytes and other lymphoma cell lines compared to freshly isolated lymphocytes, while T-lymphocyte mitogens, such as concanavalin A, increased PICOT expression concomitantly with the induction of a faster T-lymphocyte growth rate. Finally, immunohistochemistry of freshly-isolated lymph nodes from Hodgkin's lymphoma patients revealed significantly higher levels of PICOT in Hodgkin's cells, compared to the normal surrounding lymphocytes. The present results show a direct correlation between PICOT expression levels and increased cell growth, both in vitro and in vivo, and suggest that immunostaining of PICOT might be useful for in situ identification of transformed cells, such as those of Hodgkin's lymphoma.
PICOT 最初在人类 Jurkat T 淋巴细胞中被发现是一种蛋白激酶 C(PKC)结合蛋白,在其中它被发现调节 PKCtheta 依赖性功能。此外,RT-PCR 分析表明 PICOT 在广泛的器官和细胞类型中表达,包括缺乏 PKCtheta 的细胞。我们旨在分析 PICOT 蛋白在小鼠淋巴器官中的表达,并将其与 Jurkat T 淋巴细胞和其他细胞系进行比较。我们还分析了 T 淋巴细胞中 PICOT 的表达是否依赖于 PKCtheta 的存在,以及它是否与细胞生长速度相关。Western blot 分析表明,在所有测试的淋巴器官和细胞系中都表达了 PICOT。此外,在野生型和 PKCtheta 缺失型小鼠的淋巴器官中观察到相似的表达水平,表明 T 淋巴细胞中 PICOT 的表达独立于 PKCtheta。然而,与新鲜分离的淋巴细胞相比,Jurkat T 淋巴细胞和其他淋巴瘤细胞系中 PICOT 的表达水平更高,而 T 淋巴细胞有丝分裂原,如刀豆蛋白 A,在诱导更快的 T 淋巴细胞生长速度的同时增加 PICOT 的表达。最后,对霍奇金淋巴瘤患者新鲜分离的淋巴结进行免疫组织化学分析显示,霍奇金细胞中的 PICOT 水平明显高于周围正常淋巴细胞。这些结果表明,无论是在体外还是体内,PICOT 的表达水平与细胞生长的增加之间存在直接相关性,并表明 PICOT 的免疫染色可能有助于原位识别转化细胞,如霍奇金淋巴瘤细胞。