松子. 松子. 一种增强PI3激酶活性的核GTpase,由蛋白质4.1NN调节
1Johns Hopkins University School of Medicine, Department of Neuroscience, North Wolfe Street 21205, Baltimore, MD, USA.
Cell
|January 4, 2001
概括
一种名为PIKE (PI3Kinase Enhancer) 的新型蛋白激活了核PI3K的脂类激酶活性. 4,1N核转位的NGF刺激抑制了PIKE的发生.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 生物化学 生物化学
背景情况:
- 细胞质酸酸3-激酶 (PI3K) 被广泛研究.
- 关于核PI3K活动的监管仍然不太清楚.
研究的目的:
- 研究一种新型蛋白质PIKE (PI3Kinase Enhancer) 在调节核PI3K活动中的作用.
- 阐明神经生长因子 (NGF) 影响核PI3K信号传递的机制.
主要方法:
- 酵母双杂交查以确定PIKE结合蛋白.
- 主导阴性PIKE测定以评估其功能.
- 分析蛋白相互作用和亚细胞局部化 (例如,核转位).
- 西方涂抹检测循环素D1的表达.
主要成果:
- 核GTPase之一PIKE直接刺激核PI3K的脂类激酶活性.
- 主导阴性PIKE抑制NGF诱导的PI3K激活和环素D1上调.
- NGF治疗促进了PIKE与4.1N的相互作用,后者转移到核中.
- 过度表达4.1N或其核转位会抑制PIKE介导的PI3K激活.
结论:
- PIKE是核PI3K活动的关键调节器.
- 通过NGF介导的4.1N的核转位作为PIKE-PI3K信号传递的抑制机制.
- PIKE在生理上调节NGF诱导的核PI3K的激活.
相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...


