G 蛋白 Galphai 功能立即下游的 Smoothened 在 Hedgehog 发送信号
Stacey K Ogden1, Dennis Liang Fei, Neal S Schilling
1Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Nature
|November 7, 2008
概括
刺 (Hh) 的信号通道
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
背景情况:
- 刺 (Hh) 信号通路对发育至关重要,并与癌症有关.
- 滑化 (Smo) 蛋白对于Hh通路激活至关重要,由补丁 (Ptc) 受体调节.
- 斯莫的精确下游信号传输,特别是G蛋白的作用,仍然存在争议.
研究的目的:
- 研究G蛋白在Hh信号传导中的作用.
- 为了确定Smo是否作为正规的G蛋白结合受体 (GPCR) 起作用.
- 阐明Smo调节细胞内循环AMP水平的机制.
主要方法:
- 在Drosophila的体外和体内实验.
- 对Smo与G蛋白的相互作用进行分析.
- 测量细胞内循环AMP水平.
主要成果:
- 提出的证据支持Smo在响应Hh时激活G蛋白.
- 斯莫调节细胞内循环AMP水平.
- 结果表明Smo功能作为通过Galphai传输的正规GPCR信号.
结论:
- 在Hh通路中,Smo充当了正规的GPCR.
- G蛋白信号传递,特别是通过Galphai,是Hh通路激活的组成部分.
- 这澄清了关于Smo信号机制的长期争议.
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...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...


