Differential regulation of p34cdc2 and p33cdk2 by transforming growth factor-beta 1 in murine mammary epithelial cells.
Differential regulation of p34cdc2 and p33cdk2 by transforming growth factor-beta 1 in murine mammary epithelial cells.
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小鼠乳腺上皮细胞中转化生长因子-β 1 对 p34cdc2 和 p33cdk2 的差异调节。
DOI：
10.1002/jcb.240580415
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Leof,EB
中科院分区：
文献类型：
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作者：
Fautsch,MP;Eblen,ST;Anders,RA;Burnette,RJ;Leof,EB
细胞周期蛋白依赖性激酶（cdks）是一个蛋白质家族，其功能在细胞周期穿越中起关键作用。转化生长因子-β1（TGF-β1）是一种有效的上皮细胞生长抑制剂。由于cdks被认为是TGF-β生长抑制的可能生化标志物，我们研究了TGF-β 1对正常小鼠乳腺上皮细胞系（MME）和TGF-β-抗性MME细胞系（BG 18.2）中cdc 2和cdk 2的影响。TGF-β 1在加入后6 h内降低新合成的cdc 2蛋白水平。与新合成的cdc 2蛋白的这种减少相一致的是其磷酸化组蛋白H1的能力显著降低。激酶活性的降低不是由于cdc 2蛋白稳态水平的变化，因为cdc 2的mRNA和总蛋白水平直到加入TGF-β 1后12 h才降低。这表明cdc 2的激酶活性依赖于新合成的cdc 2蛋白。此外，另一种细胞周期蛋白依赖性激酶cdk 2的蛋白合成不受TGF-β 1的影响，但其激酶活性显著降低。因此，似乎TGF-β通过不同的机制降低cdc 2和cdk 2的激酶活性。
Cyclin‐dependent kinases (cdks) are a family of proteins whose function plays a critical role in cell cycle traverse. Transforming growth factor‐β1(TGF‐β1) is a potent growth inhibitor of epithelial cells. Since cdks have been suggested as possible biochemical markers for TGF‐β growth inhibition, we investigated the effect of TGF‐β1on cdc2 and cdk2 in a normal mouse mammary epithelial cell line (MME) and a TGF‐β‐resistant MME cell line (BG18.2). TGF‐β1decreases newly synthesized cdc2 protein levels within 6 h after addition. Coincident with this decrease in newly synthesized cdc2 protein was a marked reduction in its ability to phosphorylate histone H1. This decrease in kinase activity is not due to a change in steady‐state levels of cdc2 protein, since mRNA and total protein levels of cdc2 are not reduced until 12 h after TGF‐β1addition. This suggests that the kinase activity of cdc2 is dependent on newly synthesized cdc2 protien. Moreover, the protein synthesis of another cyclin‐dependent kinase, cdk2, is not effected by TGF‐β1addition, but its kinase activity is substantially reduced. Thus, it appears that TGF‐β decreases the kinase activity of both cdc2 and cdk2 by distinct mechanisms.