N 端肽序列的添加激活了磷酸肌醇-3-激酶催化亚基 p110α 的致癌和信号转导潜能。
Addition of N-terminal peptide sequences activates the oncogenic and signaling potentials of the catalytic subunit p110α of phosphoinositide-3-kinase.
机构信息
The Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, CA, USA.
出版信息
Cell Cycle. 2011 Nov 1;10(21):3731-9. doi: 10.4161/cc.10.21.17920.
Abstract
Addition of short (6 to 16 amino acids) peptide sequences to the N-terminus of p110α induces a gain of function. Such sequences include the common Flag, His, and VSV tags as well as random sequences. An N-terminal myristylation signal generally believed to activate p110α by providing a constitutive membrane address is also activating, if myristylation is mutationally abolished. The gain of function seen with N-terminally tagged (NTT) p110α constructs extends to signaling, oncogenic transformation and stimulation of cell growth. The activating effect of N-terminal tags requires a functional Ras-binding domain in p110α. Mutations in that domain (T208D and K227A) abolish the gains of function in oncogenicity and signaling. The dominant negative mutant of Ras, RasN17, interferes with transformation induced by NTT p110α. In contrast, binding to p85 activity is not required for cellular transformation and enhanced signaling by NTT p110α.
摘要
在 p110α 的 N 端添加短（6 到 16 个氨基酸）肽序列会导致功能获得。这些序列包括常见的 Flag、His 和 VSV 标签以及随机序列。通常认为，通过提供组成型膜定位，N 端肉豆蔻酰化信号会激活 p110α，但如果肉豆蔻酰化发生突变，则该信号也会被激活。用 N 端标记（NTT）p110α 构建体观察到的功能获得延伸到信号转导、致癌转化和刺激细胞生长。N 端标签的激活作用需要 p110α 中的功能性 Ras 结合结构域。该结构域中的突变（T208D 和 K227A）会消除致癌性和信号转导中的功能获得。Ras 的显性负突变体 RasN17 会干扰 NTT p110α 诱导的转化。相比之下，与 p85 活性的结合对于 NTT p110α 引起的细胞转化和增强的信号转导并非必需。
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