AN EXTRACELLULAR ROLE FOR CALMODULIN-LIKE ACTIVITY IN CELL-PROLIFERATION
AN EXTRACELLULAR ROLE FOR CALMODULIN-LIKE ACTIVITY IN CELL-PROLIFERATION
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DOI：
10.1042/bj2530877
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发表时间：
1988-08-01
影响因子：
4.1
通讯作者：
MACNEIL, S
中科院分区：
文献类型：
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作者：
CROCKER, G;DAWSON, RA;MACNEIL, S
1. 细胞外纯猪脑钙调素的加入对K562人白血病淋巴细胞的DNA合成和细胞增殖有调节作用。在较低的细胞密度下，钙调素显著刺激[3H]胸苷的摄取；在更高的密度下，它减小了。2. 在快速分裂的K562细胞条件培养基中检测到一种与钙调素难以区分的蛋白质。在这些细胞和一系列其他正常细胞和肿瘤细胞的条件培养基中发现的钙调素样活性浓度（250-1636 ng/ml）与在亚融合细胞中刺激DNA合成的浓度相同。3. 细胞外钙调素样活性和免疫反应性的数量在细胞从低密度到高密度的生长过程中发生变化，在同步的K562细胞中，细胞外钙调素在DNA合成之前达到峰值。细胞外钙调素浓度与培养基中乳酸脱氢酶的存在无关。4. 用琼脂糖珠固定的钙调蛋白拮抗剂或钙调蛋白抗体抑制细胞外钙调蛋白活性，可显著降低DNA合成。5. 这些数据有力地表明，钙调蛋白或一种非常密切相关的蛋白可以通过细胞外机制影响有丝分裂。
1. Addition of extracellular pure pig brain calmodulin was found to modulate DNA synthesis and cell proliferation in K562 human leukaemic lymphocytes. At lower cell densities calmodulin significantly stimulated [3H]thymidine uptake; at higher densities it decreased it. 2. A protein biochemically indistinguishable from calmodulin was detected in the cell-conditioned media of rapidly dividing K562 cells. The concentration of calmodulin-like activity found in the conditioned media of these and a range of other normal and neoplastic cells (250-1636 ng/ml) was of the same order as would stimulate DNA synthesis in subconfluent cells. 3. Amounts of extracellular calmodulin-like activity and immunoreactivity varied during cell growth from low to high density, a peak of extracellular calmodulin preceding DNA synthesis in synchronized K562 cells. Extracellular calmodulin concentrations did not correlate with the presence of lactate dehydrogenase in the medium. 4. Inhibition of extracellular calmodulin activity by calmodulin antagonist immobilized on agarose beads, or by antibody to calmodulin, significantly decreased DNA synthesis. 5. These data strongly suggest that calmodulin or a very closely related protein can influence mitosis through an extracellular mechanism.