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两类环磷酸腺苷(cAMP)类似物协同抑制用哈维-鼠肉瘤病毒(Ha-MuSV)DNA转染的NIH/3T3细胞中p21 ras蛋白的合成及表型转化。

Two classes of cAMP analogs synergistically inhibit p21 ras protein synthesis and phenotypic transformation of NIH/3T3 cells transfected with Ha-MuSV DNA.

作者信息

Tagliaferri P, Clair T, DeBortoli M E, Cho-Chung Y S

出版信息

Biochem Biophys Res Commun. 1985 Aug 15;130(3):1193-200. doi: 10.1016/0006-291x(85)91741-3.

DOI:10.1016/0006-291x(85)91741-3
PMID:2992503
Abstract

Factors that control cellular proliferation might do so by regulating quantitative expression of viral or cellular oncogenes. Since the growth regulatory effect of cAMP is well-known, the effect of cAMP on ras gene expression was examined on Ha-MuSV-transformed 13-3B-4 cells (NIH-3T3) grown in chemically defined serum-free medium. Treatment of cells with two classes of cAMP analogs which are selective for the two different cAMP-binding sites of type II protein kinase, in combination, synergistically inhibited both p21 ras protein synthesis and phenotypic transformation. The inhibition was also demonstrated with these analogs singly but at higher concentrations. The decrease in p21 synthesis was inversely correlated with an increase in the RII cAMP receptor protein, the regulatory subunit of type II protein kinase. These results suggest a role for cAMP and its receptor protein in the regulation of v-rasH oncogene expression.

摘要

控制细胞增殖的因素可能通过调节病毒或细胞癌基因的定量表达来实现。由于环磷酸腺苷(cAMP)的生长调节作用是众所周知的,因此在化学限定的无血清培养基中培养的Ha-MuSV转化的13-3B-4细胞(NIH-3T3)上检测了cAMP对ras基因表达的影响。用两类对II型蛋白激酶的两个不同cAMP结合位点具有选择性的cAMP类似物处理细胞,联合使用时可协同抑制p21 ras蛋白合成和表型转化。单独使用这些类似物时也能观察到抑制作用,但需要更高的浓度。p21合成的减少与II型蛋白激酶的调节亚基RII cAMP受体蛋白的增加呈负相关。这些结果表明cAMP及其受体蛋白在v-rasH癌基因表达的调节中起作用。

相似文献

1
Two classes of cAMP analogs synergistically inhibit p21 ras protein synthesis and phenotypic transformation of NIH/3T3 cells transfected with Ha-MuSV DNA.两类环磷酸腺苷(cAMP)类似物协同抑制用哈维-鼠肉瘤病毒(Ha-MuSV)DNA转染的NIH/3T3细胞中p21 ras蛋白的合成及表型转化。
Biochem Biophys Res Commun. 1985 Aug 15;130(3):1193-200. doi: 10.1016/0006-291x(85)91741-3.
2
Reverse transformation of Harvey murine sarcoma virus-transformed NIH/3T3 cells by site-selective cyclic AMP analogs.位点选择性环磷酸腺苷类似物对哈维鼠肉瘤病毒转化的NIH/3T3细胞的逆向转化
J Biol Chem. 1988 Jan 5;263(1):409-16.
3
Site-selective cAMP analogs induce nuclear translocation of the RII cAMP receptor protein in Ha-MuSV-transformed NIH/3T3 cells.位点选择性环磷酸腺苷类似物可诱导Ha-MuSV转化的NIH/3T3细胞中RII环磷酸腺苷受体蛋白的核转位。
FEBS Lett. 1987 Nov 30;224(2):377-84. doi: 10.1016/0014-5793(87)80488-x.
4
Harvey murine sarcoma virus: influences of coding and noncoding sequences on cell transformation in vitro and oncogenicity in vivo.哈维鼠肉瘤病毒:编码和非编码序列对体外细胞转化及体内致癌性的影响
J Virol. 1989 Mar;63(3):1384-92. doi: 10.1128/JVI.63.3.1384-1392.1989.
5
Dibutyryl cAMP inhibits expression of transformation-related properties in Kirsten murine sarcoma virus transformed Balb/c-3T3 cells despite continued presence of p21v-Ki-ras.二丁酰环磷腺苷抑制 Kirsten 小鼠肉瘤病毒转化的 Balb/c-3T3 细胞中与转化相关特性的表达,尽管 p21v-Ki-ras 持续存在。
Biochem Cell Biol. 1988 Jan;66(1):54-65. doi: 10.1139/o88-007.
6
Harvey murine sarcoma virus p21 ras protein: biological and biochemical significance of the cysteine nearest the carboxy terminus.哈维鼠肉瘤病毒p21 ras蛋白:最靠近羧基末端的半胱氨酸的生物学和生化意义
EMBO J. 1984 Nov;3(11):2581-5. doi: 10.1002/j.1460-2075.1984.tb02177.x.
7
The p21 ras C-terminus is required for transformation and membrane association.p21 ras的C末端是转化和膜结合所必需的。
Nature. 1984;310(5978):583-6. doi: 10.1038/310583a0.
8
Deletion mutants of Harvey ras p21 protein reveal the absolute requirement of at least two distant regions for GTP-binding and transforming activities.哈维鼠肉瘤病毒癌基因ras p21蛋白的缺失突变体揭示了GTP结合和转化活性对至少两个远距离区域的绝对需求。
EMBO J. 1986 Apr;5(4):679-87. doi: 10.1002/j.1460-2075.1986.tb04267.x.
9
Comparative biochemical properties of p21 ras molecules coded for by viral and cellular ras genes.由病毒和细胞ras基因编码的p21 ras分子的比较生化特性。
J Virol. 1982 Nov;44(2):509-19. doi: 10.1128/JVI.44.2.509-519.1982.
10
Cyclic AMP-independent processes mediate Kirsten sarcoma virus-induced changes in collagen production and other properties of cultured cells.不依赖环磷酸腺苷(cAMP)的过程介导了柯斯顿肉瘤病毒诱导的培养细胞胶原蛋白生成及其他特性的变化。
J Cell Physiol. 1985 Jan;122(1):113-9. doi: 10.1002/jcp.1041220117.

引用本文的文献

1
Induction of differentiation in v-Ha-ras-transformed MDCK cells by prostaglandin E2 and 8-bromo-cyclic AMP is associated with a decrease in steady-state level of inositol 1,4,5-trisphosphate.前列腺素E2和8-溴环磷酸腺苷诱导v-Ha-ras转化的MDCK细胞分化与肌醇1,4,5-三磷酸稳态水平降低有关。
Mol Cell Biol. 1990 Jan;10(1):57-67. doi: 10.1128/mcb.10.1.57-67.1990.