PIKE: A nuclear GTPase that enhances PI3Kinase activity and is regulated by protein 4.1N
PIKE: A nuclear GTPase that enhances PI3Kinase activity and is regulated by protein 4.1N
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DOI：
10.1016/s0092-8674(00)00195-1
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发表时间：
2000-12-08
期刊：
影响因子：
64.5
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Ye, KQ;Hurt, J;Snyder, SH
虽然细胞质PI3激酶（PI3K）被充分表征，但核PI3K的调节一直不清楚。PIKE（PI3 Kinase Enhancer）是一种新的蛋白质，它与细胞核中的PI3 K相互作用，从而激活其脂质激酶活性。PIKE编码753个氨基酸的核GT3。显性负性PIKE阻止NGF增强PI3K和上调细胞周期蛋白D1。NGF处理还导致PIKE与4.1N的相互作用，其已经易位到细胞核，这与基于其在酵母双杂交筛选中结合4.1N的PIKE的初始鉴定相符。4.1N的过表达消除了PIKE对PI3K的影响。PIKE对核PI3K的激活被NGF刺激的4.1N易位到核中所抑制。因此，PIKE生理性地调节NGF对核PI3K的激活。
While cytoplasmic PI3Kinase (PI3K) is well characterized, regulation of nuclear PI3K has been obscure. A novel protein, PIKE (PI3Kinase Enhancer), interacts with nuclear PI3K to stimulate its lipid kinase activity. PIKE encodes a 753 amino acid nuclear GTPase. Dominant-negative PIKE prevents the NGF enhancement of PI3K and upregulation of cyclin D1. NGF treatment also leads to PIKE interactions with 4.1N, which has translocated to the nucleus, fitting with the initial identification of PIKE based on its binding 4.1N in a yeast two-hybrid screen. Overexpression of 4.1N abolishes PIKE effects on PI3K. Activation of nuclear PI3K by PIKE is inhibited by the NGF-stimulated 4.1N translocation to the nucleus. Thus, PIKE physiologically modulates the activation by NGF of nuclear PI3K.