Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors.

Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors.
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带有适当表面受体的细胞中表皮生长因子、神经生长因子和血小板衍生生长因子的染色质结合。

DOI:
10.1073/pnas.83.11.3728
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发表时间:
1986
影响因子:
11.1
通讯作者:
Koprowski,H
Koprowski,H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Rakowicz-Szulczynska,EM;Rodeck,U;Herlyn,M;Koprowski,H

文献摘要

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我们分析了125碘标记的表皮生长因子,神经生长因子,血小板衍生生长因子在不同的细胞系,表达或不表达这些因子的各自的表面受体的摄取和细胞内分布。孵育1小时后,在细胞质部分和细胞核中检测到所有三种生长因子,与染色质紧密结合。染色质结合的生长因子的量在孵育期间继续增加,并且在48小时的分析显示每个染色质结合的标记生长因子处于未降解形式。用DNase II(10-20%消化序列)有限消化染色质后,仅在孵育1小时后检测到所有三种生长因子的特异性释放,但在24和48小时后未检测到,表明参与生长因子结合的DNA区域变得具有核酸酶抗性。标记的表皮生长因子和神经生长因子与分离的染色质的结合被各自生长因子受体特异性的单克隆抗体抑制。这些数据表明,染色质结合可能是生长因子作用途径中的重要步骤。
We analyzed the uptake and intracellular distribution of 125I-labeled epidermal growth factor, nerve growth factor, and platelet-derived growth factor in different cell lines that express or do not express the respective surface receptors for these factors. After 1 hr of incubation, all three growth factors were detected in the cytoplasmic fraction and in the nucleus, tightly bound to chromatin. The amount of chromatin-bound growth factors continued to increase during the incubation, and analysis at 48 hr revealed each chromatin-bound labeled growth factor in a nondegraded form. After limited digestion of chromatin with DNase II (10-20% digested sequences), specific release of all three growth factors was detected only after 1 hr of incubation but not after 24 and 48 hr, suggesting that the DNA regions involved in growth factor binding became nuclease-resistant. Binding of labeled epidermal growth factor and nerve growth factor to isolated chromatin was inhibited by monoclonal antibodies specific for the respective growth factor receptor. The data suggest that chromatin binding may represent an important step in the pathway of growth factor action.