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Pike tyrosine phosphorylation regulates its apoptotic cleavage during programmed cell death

机译:派克酪氨酸磷酸化在程序性细胞死亡过程中调节其凋亡裂解

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摘要

PIKE (PI 3-kinase enhancer) is a nuclear GTPase that enhances PI 3-kinase activity. NGF treatment elicits the membrane-associated 4. IN nuclear translocation and binds PIKE, which was initially identified as a 4. IN binding partner in a yeast two-hybrid screening. The binding of 4.IN to PIKE prevents its interactions with nuclear PI 3-kinase, leading to inactivation of PI 3-kinase (Ye et al., 2000). In addition to interacting with protein 4.IN and PI 3-kinase, PIKE-S also robustly associates with PLC-yl, which acts as a physiological guanine-nucleotide-exchange factor (GEF) for PIKE-S through its SH3 domain, and the phospholipase catalytic activity is not required (Ye et al., 2002). NGF elicits PLC-yl nuclear translocation and interaction with PIKE-S. The third proline-rich domain of PIKE-S binds directly to PLC-gammal's SH3 domain. The finding that the PLC-yl SH3 domain is a physiological GEF for PIKE-S indicates that this domain can display biological activity, which might account for its mitogenic activity. Thus, the SH3 domain but not the phospholipase catalytic activity of PLC-yl is necessary for its mitogenic actions, probably through activating nuclear PI 3-kinase.
机译:PIKE(PI 3-激酶增强剂)是一种核GTP酶,可增强PI 3-激酶活性。 NGF处理引起膜相关的4.IN核易位并结合PIKE,PIKE在酵母双杂交筛选中最初被鉴定为4.IN结合伴侣。 4.IN与PIKE的结合阻止了其与核PI 3-激酶的相互作用,导致PI 3-激酶失活(Ye等,2000)。除了与蛋白质4.IN和PI 3-激酶相互作用外,PIKE-S还与PLC-yl牢固结合,PLC-yl通过其SH3结构域充当PIKE-S的生理鸟嘌呤核苷酸交换因子(GEF),并且不需要磷脂酶的催化活性(Ye等,2002)。 NGF引发PLC-yl核易位并与PIKE-S相互作用。 PIKE-S的第三个富含脯氨酸的域直接与PLC-gammal的SH3域结合。 PLC-yl SH3结构域是PIKE-S的生理学GEF的发现表明,该结构域可以显示生物活性,这可能是其促有丝分裂活性的原因。因此,SH3结构域而不是PLC-yl的磷脂酶催化活性对其有丝分裂作用是必需的,可能是通过激活核PI 3-激酶来实现的。

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