Interleukin-2 induces proliferation of T lymphocyte mutants lacking protein kinase C.
Interleukin-2 induces proliferation of T lymphocyte mutants lacking protein kinase C.
复制标题
Interleukin-2 诱导缺乏蛋白激酶 C 的 T 淋巴细胞突变体增殖。
DOI：
10.1016/0092-8674(88)90012-8
复制
发表时间：
1988
期刊：
影响因子：
64.5
通讯作者：
Gelfand,EW
中科院分区：
文献类型：
--
作者：
Mills,GB;Girard,P;Grinstein,S;Gelfand,EW
我们已经确定了一个小鼠T淋巴细胞克隆，明显缺乏二酰基甘油和磷脂活化蛋白激酶C (PKC)：细胞提取物不显示磷脂酰丝氨酸、CaZ+或磷酸酯依赖的磷酸转移酶活性；在pkc特异性抗体的免疫印迹中未检测到该酶；在完整细胞中检测不到phobol酯结合位点；PKC的激活剂不会刺激完整细胞的增殖或Na+/H+交换。正常小鼠T淋巴细胞中仅检测到PKC β mRNA。突变T淋巴细胞含有与正常小鼠淋巴细胞相似的4.4 kb PKC β信息，但在正常淋巴细胞中发现的2.9 kb和1.2 kb信息几乎无法检测到。在Southern分析中没有检测到异常，这表明异常可能是在信息拼接或稳定性的水平上。由于PKC缺陷细胞对T淋巴细胞生长因子白介素-2的增殖反应，我们得出结论，PKC的激活对白介素-2的促生长作用不是必需的。蛋白激酶C （PKC）以两种形式发生，一种是天然的80 kd分子，另一种是较小的蛋白水解片段（Kikkawa和Nishizuka， 1986）。天然酶在Ca2+、磷脂酰丝氨酸、二酰基甘油（dag）或磷酯（如12- o -十四烷基磷酯- 13-乙酸酯（TPA））存在的情况下磷酸化底物，而不是在Ca2+、磷脂酰丝氨酸和二酰甘油（dag）存在的情况下磷酸化底物
We have identified a murine T lymphocyte clone that apparently lacks diacylglycerol-and phospholipidactivated protein kinase C (PKC): cell extracts do not display phosphatidylserine, CaZ+, or phorbol esterdependent phosphotransferase activity; the enzyme was not detected in immunoblots with PKC-specific antibodies; phorbol ester binding sites are not detectable in intact cells; and activators of PKC do not stimulate proliferation or Na+/H+ exchange in intact cells. Only PKC beta mRNA was detected in normal murine T lymphocytes. The mutant T lymphocytes contained amounts of 4.4 kb PKC beta message similar to those in normal murine lymphocytes, but the 2.9 kb and 1.2 kb messages found in normal lymphocytes were barely detectable. No abnormalities were detected on Southern analysis, suggesting that the abnormality may be at the level of message splicing or stability. Since PKC-deficient cells proliferate in response to the T lymphocyte growth factor, interleukin-2, we conclude that activation of PKC is not essential for the growth-promoting action of interleukin-2. tntroductionProtein kinase C (PKC) occurs in two forms, a native 80 kd molecule and a smaller proteolytic fragment (reviewed in Kikkawa and Nishizuka, 1986). The native enzyme phosphorylates substrates in the presence but not the absence of Ca2+, phosphatidylserine, and diacylglycerols (DAGs), or phorbol esters, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), that bind to the same allosteric