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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cell cycle-dependent regulation of p185neu: a relationship between disruption of this regulation and transformation.
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Cell cycle-dependent regulation of p185neu: a relationship between disruption of this regulation and transformation.

机译：p185neu的细胞周期依赖性调节：这种调节的破坏与转化之间的关系。

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摘要

Structure and function of p185neu receptor tyrosine kinase were found to be regulated in a cell cycle-dependent manner. In M phase, p185neu is hyperphosphorylated at serine and/or threonine residues. The phosphotyrosine [Tyr(P)] content of p185neu is at its highest level in G0/G1 phase, decreases through S and G2 phases, and reaches its lowest level in M phase. Phospholipase C-gamma (PLC-gamma) and GTPase-activating protein (GAP), substrates of p185neu, also have a similar profile of Tyr(P) content during the cell cycle. These results, along with in vitro immune complex kinase assays, suggest that the tyrosine kinase activity of p185neu is least active in M phase. Interestingly, the mutation-activated neu oncogene (neu*)-encoded protein product, p185neu* escaped from cell cycle regulation. Taken together, we demonstrate in this report that the structure and function of p185neu are regulated in a cell cycle-dependent manner, yet p185neu* escapes from this regulation and remains active through the cell cycle. Disruption of this cell cycle regulation may define a mechanism for p185neu*-mediated cellular transformation.
机译：发现p185neu受体酪氨酸激酶的结构和功能以细胞周期依赖性方式被调节。在M期，p185neu在丝氨酸和/或苏氨酸残基上被过度磷酸化。 p185neu的磷酸酪氨酸[Tyr（P）]含量在G0 / G1相中达到最高水平，在S和G2相中降低，在M相中达到最低水平。磷脂酶C-γ（PLC-γ）和GTPase激活蛋白（GAP）是p185neu的底物，在细胞周期中也具有类似的Tyr（P）含量特征。这些结果以及体外免疫复合激酶测定表明p185neu的酪氨酸激酶活性在M期最不活跃。有趣的是，突变激活的神经致癌基因（neu *）编码的蛋白产物p185neu *从细胞周期调控中逃脱了。综上所述，我们在本报告中证明p185neu的结构和功能以细胞周期依赖性方式调节，但p185neu *逃避了这种调节并在整个细胞周期中保持活跃。这种细胞周期调控的破坏可能会定义p185neu *介导的细胞转化的机制。

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