PIKE GTPase: a novel mediator of phosphoinositide signaling
PIKE GTPase: a novel mediator of phosphoinositide signaling
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DOI：
10.1242/jcs.00924
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发表时间：
2004-01-15
影响因子：
4
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Ye, KQ;Snyder, SH
磷脂酰肌醇（PI）3-激酶增强子（PIKE）是脑特异性的GT3，其结合PI 3-激酶并刺激其脂质激酶活性。它以两种形式存在：第一个被鉴定的PIKE-S较短，并且仅在细胞核内;相反，较长的形式PIKE-L存在于多个细胞内区室中。神经生长因子治疗通过触发磷脂酶C（PLC）-γ 1的核转位导致PIKE-S活化，所述磷脂酶C（PLC）-γ 1通过其Src同源物3（SH 3）结构域充当PIKE-S的生理性鸟嘌呤核苷酸交换因子（GEF）。细胞质PI 3-激酶及其脂质产物磷脂酰肌醇（3，4，5）-三磷酸[PtdIns（3，4，5）P-3]通过结合到它们的普列克底物蛋白同源（PH）结构域来调节许多信号分子的膜转位和活化。然而，人们对它们的核对应物的生理作用知之甚少。核PLC-γ 1/PIKE-S/PI 3-激酶信号通路似乎是细胞质PLC-γ 1和PI 3-激酶之间串扰的延伸。PIKE-L含有C-末端延伸，其由ADP核糖基化-GTP酶激活蛋白（ArfGAP）结构域和两个锚蛋白重复序列以及N-末端GTP酶结构域组成。PIKE-L可能具有额外的细胞核功能，包括通过代谢型谷氨酸受体调节突触后信号传导。
Phosphoinositide (PI) 3-kinase enhancer (PIKE) is a brain-specific GTPase that binds to PI 3-kinase and stimulates its lipid kinase activity. It exists in two forms: the first to be identified, PIKE-S, is shorter and exclusively nuclear; by contrast, the longer form, PIKE-L, resides in multiple intracellular compartments. Nerve growth factor treatment leads to PIKE-S activation by triggering the nuclear translocation of phospholipase C (PLC)-gamma1, which acts as a physiological guanine nucleotide exchange factor (GEF) for PIKE-S through its Src-homlogy 3 (SH3) domain. Cytoplasmic PI 3-kinase and its lipid product phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P-3] regulate the membrane translocation and activation of many signaling molecules by binding to their pleckstrin homology (PH) domains. However, little is known about the physiological roles of their nuclear counterparts. The nuclear PLC-gamma1/PIKE-S/PI 3-kinase signaling pathway seems to be an extension of the crosstalk between cytoplasmic PLC-gamma1 and PI 3-kinase. PIKE-L contains a C-terminal extension consisting of an ADP ribosylation-GTPase-activating protein (ArfGAP) domain and two ankyrin repeats in addition to the N-terminal GTPase domain. PIKE-L could have additional, extranuclear functions, including regulation of postsynaptic signaling by metabotropic glutamate receptors.