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血小板衍生生长因子刺激瑞士小鼠3T3细胞中活性p21ras.GTP复合物的形成。

Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells.

作者信息

Satoh T, Endo M, Nakafuku M, Nakamura S, Kaziro Y

机构信息

Institute of Medical Science, University of Tokyo, Japan.

出版信息

Proc Natl Acad Sci U S A. 1990 Aug;87(15):5993-7. doi: 10.1073/pnas.87.15.5993.

DOI:10.1073/pnas.87.15.5993
PMID:2198577
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC54456/
Abstract

The ras gene product (p21) is a GTP-binding protein and is thought to play an important role in signal transduction of growth and differentiation in many types of mammalian cells. The p21.GTP complex is an active conformation, as described previously for polypeptide chain elongation factors (EF-Tu and EF-G) and heterotrimeric GTP-binding proteins (G proteins). In the study reported here, we measured the amounts of p21-bound guanine nucleotides under various conditions in the G54 cell line, a derivative of Swiss 3T3 cells that overexpresses normal c-Ha-ras. More p21.GTP complexes were present in growing cells than in quiescent cells. When quiescent cells were stimulated with fetal bovine serum to promote DNA synthesis, p21.GTP increased approximately 2-fold. Among a number of purified growth factors, platelet-derived growth factor enhanced the formation of p21.GTP, whereas the combination of bombesin and insulin, which also induces DNA synthesis, did not. These results strongly suggest that p21 is a transducer of the growth signal from the platelet-derived growth factor receptor in Swiss 3T3 cells and that the signal is transmitted through a p21.GTP complex.

摘要

ras基因产物(p21)是一种GTP结合蛋白,被认为在多种哺乳动物细胞的生长和分化信号转导中起重要作用。如先前针对多肽链延伸因子(EF-Tu和EF-G)和异三聚体GTP结合蛋白(G蛋白)所描述的那样,p21.GTP复合物是一种活性构象。在本文报道的研究中,我们在G54细胞系(一种过表达正常c-Ha-ras的瑞士3T3细胞衍生物)的各种条件下测量了与p21结合的鸟嘌呤核苷酸的量。与静止细胞相比,生长细胞中存在更多的p21.GTP复合物。当用胎牛血清刺激静止细胞以促进DNA合成时,p21.GTP增加了约2倍。在许多纯化的生长因子中,血小板衍生生长因子增强了p21.GTP的形成,而同样诱导DNA合成的蛙皮素和胰岛素的组合则没有。这些结果强烈表明,p21是瑞士3T3细胞中来自血小板衍生生长因子受体的生长信号的转导器,并且该信号通过p21.GTP复合物进行传递。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/cb0af38ca7cb/pnas01040-0417-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/0bbffe804309/pnas01040-0415-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/0d37688e6392/pnas01040-0416-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/6196d6d6c648/pnas01040-0416-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/cb0af38ca7cb/pnas01040-0417-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/0bbffe804309/pnas01040-0415-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/0d37688e6392/pnas01040-0416-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/6196d6d6c648/pnas01040-0416-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b980/54456/cb0af38ca7cb/pnas01040-0417-a.jpg

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本文引用的文献

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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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Ras history: The saga continues.Ras的历程:传奇仍在继续。
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p27Kip1 inhibition of GRB2-SOS formation can regulate Ras activation.p27Kip1对GRB2 - SOS形成的抑制作用可调节Ras激活。
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Ras activity late in G1 phase required for p27kip1 downregulation, passage through the restriction point, and entry into S phase in growth factor-stimulated NIH 3T3 fibroblasts.在生长因子刺激的NIH 3T3成纤维细胞中,G1期晚期的Ras活性是p27kip1下调、通过限制点以及进入S期所必需的。
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Induction of neurite formation in PC12 cells by microinjection of proto-oncogenic Ha-ras protein preincubated with guanosine-5'-O-(3-thiotriphosphate).通过显微注射与鸟苷-5'-O-(3-硫代三磷酸)预孵育的原癌基因Ha-ras蛋白诱导PC12细胞形成神经突。
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ras genes.RAS基因
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NIH-3T3 cells transformed by the EJ-ras oncogene exhibit reduced platelet-derived growth factor-mediated Ca2+ mobilization.由EJ - ras癌基因转化的NIH - 3T3细胞表现出血小板衍生生长因子介导的Ca2+动员减少。
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4345-9. doi: 10.1073/pnas.85.12.4345.
7
Malignant transformation by ras and other oncogenes produces common alterations in inositol phospholipid signaling pathways.Ras及其他癌基因引起的恶性转化会导致肌醇磷脂信号通路发生常见改变。
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Temporal relationship between inositol polyphosphate formation and increases in cytosolic Ca2+ in quiescent 3T3 cells stimulated by platelet-derived growth factor, bombesin and vasopressin.血小板衍生生长因子、蛙皮素和血管加压素刺激静止3T3细胞时,肌醇多磷酸形成与胞质Ca2+增加之间的时间关系。
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Characterization of a factor that stimulates hydrolysis of GTP bound to ras gene product p21 (GTPase-activating protein) and correlation of its activity to cell density.一种刺激与ras基因产物p21结合的GTP水解的因子(GTP酶激活蛋白)的特性及其活性与细胞密度的相关性。
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