Internalized basic fibroblast growth factor translocates to nuclei of venular endothelial cells.
Internalized basic fibroblast growth factor translocates to nuclei of venular endothelial cells.
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内化的碱性成纤维细胞生长因子易位至小静脉内皮细胞的细胞核。
DOI：
10.1152/ajpheart.1992.262.5.h1525
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Granger,HJ
中科院分区：
文献类型：
--
作者：
HawkerJr,JR;Granger,HJ
为了开始了解碱性成纤维细胞生长因子 (bFGF) 刺激冠状静脉内皮细胞 (CVEC) 增殖的分子机制，我们表征了 bFGF 与 CVEC 上各个结合位点的动力学相互作用，并确定了 bFGF 核转位的动力学。我们报告说，bFGF 快速与其受体结合，并在 37°C 下立即内化，受体结合的半衰期为 0.9 分钟。内化后，bFGF 通过两条动力学和生化上可区分的途径进行加工。高达 40-50% 的总内化 bFGF 在早期时间点（0-2 小时）易位至血清饥饿的静止细胞的细胞核。到 24 小时，这一比例下降至小于或等于 20%。细胞质积累持续增加长达 24 小时。核结合 125I 标记的 bFGF 主要由完整的 18-kDa 物质和少量 16-kDa 降解片段组成。核结合的 125I 标记的 bFGF 即使在 24 小时后也几乎没有显示出降解的证据，而细胞质的 125I 标记的 bFGF 随着时间的推移显示出越来越多的降解，形成更小的片段。 bFGF 的核结合在 DNA 合成开始前 8 小时达到平衡，DNA 合成在添加生长因子后 9-12 小时开始。这些结果表明，在生长因子与细胞表面受体结合后，核结合的 bFGF 可能在触发 CVEC 分裂（增殖）中发挥作用。
To begin to understand the molecular mechanisms by which basic fibroblast growth factor (bFGF) stimulates proliferation of coronary venular endothelial cells (CVEC), we have characterized the kinetic interactions of bFGF with various binding sites on CVEC and determined the kinetics of nuclear translocation of bFGF. We report that bFGF rapidly binds to its receptor and is immediately internalized at 37 degrees C with a half-time for receptor binding of 0.9 min. After internalization bFGF is processed by two kinetically and biochemically distinguishable pathways. Up to 40-50% of total internalized bFGF is translocated to the nuclei of serum-starved, quiescent cells at early time points (0-2 h). This proportion declines to less than or equal to 20% by 24 h. Cytoplasmic accumulation continued to increase for up to 24 h. Nuclear-bound 125I-labeled bFGF consisted primarily of the intact 18-kDa species with small amounts of a 16-kDa degradation fragment. Nuclear-bound 125I-labeled bFGF showed little evidence of degradation even after 24 h, whereas cytoplasmic 125I-labeled bFGF showed increased degradation to smaller fragments with time. Nuclear-binding of bFGF reached equilibrium by 8 h, just before initiation of DNA synthesis, which began 9-12 h after growth factor addition. These results suggest that nuclear-bound bFGF may function in triggering division (proliferation) of CVEC subsequent to binding of the growth factor to cell surface receptors.