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显性抑制性Ha-ras突变对PC12细胞神经元分化的影响。

Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells.

作者信息

Szeberényi J, Cai H, Cooper G M

机构信息

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.

出版信息

Mol Cell Biol. 1990 Oct;10(10):5324-32. doi: 10.1128/mcb.10.10.5324-5332.1990.

DOI:10.1128/mcb.10.10.5324-5332.1990
PMID:2118994
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC361225/
Abstract

A dominant inhibitory mutation of Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21 (Asn-17)Ha-ras] has been used to investigate the role of ras in neuronal differentiation of PC12 cells. The growth of PC12 cells, in contrast to NIH 3T3 cells, was not inhibited by p21(Asn-17)Ha-ras expression. However, PC12 cells expressing the mutant Ha-ras protein showed a marked inhibition of morphological differentiation induced by nerve growth factor (NGF) or fibroblast growth factor (FGF). These cells, however, were still able to respond with neurite outgrowth to dibutyryl cyclic AMP and 12-O-tetradecanoylphorbol-13-acetate (TPA). Induction of early-response genes (fos, jun, and zif268) by NGF and FGF but not by TPA was also inhibited by high levels of p21(Asn-17)Ha-ras. However, lower levels of p21(Asn-17) expression were sufficient to block neuronal differentiation without inhibiting induction of these early-response genes. Induction of the secondary-response genes SCG10 and transin by NGF, like morphological differentiation, was inhibited by low levels of p21(Asn-17) whether or not induction of early-response genes was blocked. Therefore, although inhibition of ras function can inhibit early-response gene induction, this is not required to block morphological differentiation or secondary-response gene expression. These results suggest that ras proteins are involved in at least two different pathways of signal transduction from the NGF receptor, which can be distinguished by differential sensitivity to p21(Asn-17)Ha-ras. In addition, ras and protein kinase C can apparently induce early-response gene expression by independent pathways in PC12 cells.

摘要

一种显性抑制性Ha-ras突变，可将基因产物p21中的Ser-17变为Asn-17 [p21(Asn-17)Ha-ras]，已被用于研究ras在PC12细胞神经元分化中的作用。与NIH 3T3细胞不同，PC12细胞的生长不受p21(Asn-17)Ha-ras表达的抑制。然而，表达突变型Ha-ras蛋白的PC12细胞表现出对神经生长因子(NGF)或成纤维细胞生长因子(FGF)诱导的形态分化有明显抑制作用。然而，这些细胞仍能对二丁酰环磷酸腺苷和12-O-十四烷酰佛波醇-13-乙酸酯(TPA)产生神经突生长反应。高水平的p21(Asn-17)Ha-ras也抑制了NGF和FGF而非TPA诱导的早期反应基因(fos、jun和zif268)。然而，较低水平的p21(Asn-17)表达足以阻断神经元分化，而不抑制这些早期反应基因的诱导。NGF诱导的二级反应基因SCG10和转胶酶，与形态分化一样，无论早期反应基因的诱导是否被阻断，低水平的p21(Asn-17)都能抑制其表达。因此，尽管抑制ras功能可以抑制早期反应基因的诱导，但这并不是阻断形态分化或二级反应基因表达所必需的。这些结果表明，ras蛋白参与了至少两条从NGF受体发出的不同信号转导途径，这两条途径可通过对p21(Asn-17)Ha-ras的不同敏感性来区分。此外，ras和蛋白激酶C显然可以通过PC12细胞中的独立途径诱导早期反应基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/73c31bd3f677/molcellb00046-0314-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/34d8523fce9f/molcellb00046-0310-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/f4774f00ab41/molcellb00046-0311-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/e6d3a2525027/molcellb00046-0312-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/172e8149cb94/molcellb00046-0313-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/5d69b5e7443c/molcellb00046-0313-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/73c31bd3f677/molcellb00046-0314-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/34d8523fce9f/molcellb00046-0310-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/f4774f00ab41/molcellb00046-0311-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/e6d3a2525027/molcellb00046-0312-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/172e8149cb94/molcellb00046-0313-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/5d69b5e7443c/molcellb00046-0313-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/095f/361225/73c31bd3f677/molcellb00046-0314-a.jpg

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本文引用的文献

1
Structure of mouse metallothionein-I gene and its mRNA.小鼠金属硫蛋白-I基因及其mRNA的结构。
Nature. 1981 Jul 16;292(5820):267-9. doi: 10.1038/292267a0.
2
Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein.通过显微注射Ha-ras p21蛋白对NIH 3T3细胞进行转化。
Nature. 1984;310(5977):508-11. doi: 10.1038/310508a0.
3
Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells.显微注射人H-ras（T-24）蛋白的致癌基因形式会导致静止细胞快速增殖。
Egr1在与PC12细胞神经元分化相关的转录程序中的作用。
PLoS One. 2017 Jan 11;12(1):e0170076. doi: 10.1371/journal.pone.0170076. eCollection 2017.
4
Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein.硝普钠，一种一氧化氮供体，不能克服显性负性 Ras 蛋白对 PC12 细胞神经分化的阻断作用。
Cell Mol Biol Lett. 2012 Sep;17(3):323-32. doi: 10.2478/s11658-012-0013-8. Epub 2012 Apr 10.
5
Global expression analysis identified a preferentially nerve growth factor-induced transcriptional program regulated by sustained mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and AP-1 protein activation during PC12 cell differentiation.全球表达分析鉴定了一个优先的神经生长因子诱导的转录程序，该程序在 PC12 细胞分化过程中受到持续的丝裂原活化蛋白激酶/细胞外信号调节激酶 (ERK) 和 AP-1 蛋白激活的调节。
J Biol Chem. 2011 Dec 30;286(52):45131-45. doi: 10.1074/jbc.M111.274076. Epub 2011 Nov 7.
6
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10
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4
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6
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Cell. 1984 Aug;38(1):29-38. doi: 10.1016/0092-8674(84)90523-3.
7
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8
Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells.NIH 3T3细胞血清刺激生长过程中ras原癌基因功能的需求
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9
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Epidermal growth factor and oncogenes induce transcription of the same cellular mRNA in rat fibroblasts.表皮生长因子和癌基因可诱导大鼠成纤维细胞中相同细胞信使核糖核酸的转录。
EMBO J. 1985 Jun;4(6):1435-40. doi: 10.1002/j.1460-2075.1985.tb03799.x.