Essential role of the tyrosine kinase substrate phospholipase C-gamma 1 in mammalian growth and development

Essential role of the tyrosine kinase substrate phospholipase C-gamma 1 in mammalian growth and development
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DOI:
10.1073/pnas.94.7.2999
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发表时间:
1997-04-01
影响因子:
11.1
通讯作者:
Carpenter, G
Carpenter, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ji, QS;Winnier, GE;Carpenter, G

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许多酪氨酸激酶的激活导致磷脂酶 C-gamma 1 (PLC-gamma 1) 的磷酸化和激活,为了检查该蛋白的生物学功能,使用同源重组选择性破坏小鼠中的 Plcg1 基因,Plcg1 的纯合破坏导致胚胎在大约胚胎日 (E) 9.0 时致死,组织学分析表明 Plcg1 (-/-)胚胎在 E 8.5 时表现正常,但在 E 8.5-E9.0 之后无法继续正常发育和生长。这些结果清楚地表明,PLC-gamma 1 具有动员第二信使分子的能力,是一种重要的信号转导分子,其缺失不能通过其他信号传导途径或编码 PLC 同工酶的其他基因来补偿。
The activation of many tyrosine kinases leads to the phosphorylation and activation of phospholipase C-gamma 1 (PLC-gamma 1), To examine the biological function of this protein, homologous recombination has been used to selectively disrupt the Plcg1 gene in mice, Homozygous disruption of Plcg1 results in embryonic lethality at approximately embryonic day (E) 9.0, Histological analysis Indicates that Plcg1 (-/-) embryos appear normal at E 8.5 but fail to continue normal development and growth beyond E 8.5-E9.0. These results clearly demonstrate that PLC-gamma 1 with, by inference, its capacity to mobilize second messenger molecules is an essential signal transducing molecule whose absence is not compensated by other signaling pathways or other genes encoding PLC isozymes.