Nuclear localization of protein kinase C.
Nuclear localization of protein kinase C.
复制标题
蛋白激酶 C 的核定位。
DOI：
10.1042/bst0210879
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发表时间：
1993
影响因子：
3.9
通讯作者：
Raben,DM
中科院分区：
文献类型：
--
作者：
Leach,KL;Raben,DM
定义信号转导途径的一个关键问题是了解在质膜上产生的信号如何传递到细胞核。许多研究都暗示了蛋白激酶C （PKC）在细胞核功能中的作用。例如，许多基因的转录，包括c-fos和编码纤溶酶原激活剂、干扰素和白介素-2的基因，通过PKC的激活剂phorbol酯处理细胞而增加[1-41]。12-肉豆蔻酸13-醋酸酯（phorbol 12-myristate 13-acetate， PMA）可刺激多种核蛋白的磷酸化，如层合蛋白3、基质蛋白和DNA拓扑异构酶11，这表明PKC可能直接磷酸化这些蛋白，从而调节其功能[S-71]。通过免疫学和生化分析，我们和其他人已经证明PKC存在于肝脏[HI， HIA0细胞，[9]和3T3细胞]的细胞核中[lo-121]。在某些系统中，如肝脏，PKC似乎在细胞核中组成性表达[HI]。相反，在其他细胞系统中，PKC存在于受刺激细胞制备的细胞核中，而不存在于未受刺激细胞中。核定位的刺激不仅来自于PMA的处理，也来自于有丝分裂原如血小板衍生生长因子、胰岛素样生长因子-1和a-凝血酶的细胞孵育[11-13]。PMA的作用可能是由PKC的直接激活引起的，但分裂原导致核PKC水平升高的机制尚不清楚。在本文中，我们将回顾我们的结果，证明PKC在两种不同的细胞系，NIH 3T3细胞和IIC9细胞中的核定位[1,131]。用PMA处理任何一种细胞类型都会导致细胞核中PKC水平的增加。在IIC9细胞中，我们也证明了用生理激动剂a-凝血酶治疗可以刺激核定位。此外，我们已经使用IIC9系统开始解决a-凝血素诱导PKC核的机制
A key issue in defining signal transduction pathways is understanding how signals generated at the plasma membrane are communicated to the nucleus. A number of studies have implicated a role for protein kinase C (PKC) in nuclear function. For example, the transcription of many genes, including c-fos and those coding for plasminogen activator, interferon and interleukin-2, is increased by the treatment of cells with phorbol esters, activators of PKC [1-41. Phosphorylation of a number of nuclear proteins, such as lamin€ 3, matrix proteins and DNA topoisomerase 11, is stimulated by phorbol 12-myristate 13-acetate (PMA), suggesting that PKC may be phosphorylating these proteins directly, and thereby regulating their function [S-71. llsing immunological and biochemical analyses, we and others have demonstrated the presence of PKC in the nuclei in liver [HI, HIA0 cells [9] and 3T3 cells [lo-121. In some systems, such as the liver, PKC appears to be constitutively expressed in the nucleus [HI. In contrast, in other cell systems, PKC is present in nuclei prepared from stimulated, but not unstimulated cells. Stimulation of nuclear localization results not only from treatment with PMA, but also from incubation of cells with mitogens such as platelet-derived growth factor, insulin-like growth factor-I and a-thrombin [11-13]. The effect of PMA may result from a direct activation of PKC, but the mechanisms by which mitogens result in increased levels of nuclear PKC are not known.In this paper we will review our results demonstrating nuclear localization of PKC in two different cell lines, NIH 3T3 cells, and IIC9 cells [lo, 131. Treatment of either cell type with PMA results in increased levels of PKC in the nucleus. In the IIC9 cells, we have also demonstrated that treatment with the physiological agonist a-thrombin stimulates nuclear localization. Furthermore, we have used the IIC9 system to begin to address the mechanisms for a-thrombin-induced PKC nuclear