相关实验视频
Updated: Aug 24, 2025

08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
18.5K
在内体中非正规的β-上腺激活
Yonghoon Kwon1, Sohum Mehta1, Mary Clark1
1Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
Nature
|October 26, 2022
概括
G蛋白结合受体 (GPCR) 信号激活来自内体的细胞外信号调节激酶 (ERK),而不是血膜. 这种空间控制通过调节核ERK活动影响细胞增殖.
科学领域:
- 细胞信号传输
- 分子生物学
- 受体生物学
背景情况:
- G蛋白结合受体 (GPCR) 是关键的信号分子和药物标.
- GPCRs激活细胞外信号调节激酶 (ERK),这是细胞增殖和生存的关键调节剂.
- 经GPCR介导的ERK激活的确切机制尚不清楚.
研究的目的:
- 研究控制ERK激活中的β2上腺体受体 (β2AR) 信号的空间组织.
- 阐明内体信号在GPCR介导的细胞反应中的作用.
主要方法:
- 使用以细胞为目标的ERK活动生物传感器.
- 研究了β2AR信号,内细胞和Gαs局部化.
- 使用药物抑制内体信号通路.
主要成果:
- 2AR信号诱导的ERK活动特定于内分泌体,而不是血膜.
- 内体ERK活性取决于内体局部化的Gαs和β2AR内细胞分裂.
- 确定了一个非正规的内体Gαs-RAF-MAPK轴,控制核ERK,MYC表达和细胞增殖.
结论:
- 透露了通过GPCR信号的ERK空间调节的非正规机制.
- 显示功能显著的内体信号轴控制细胞增殖.
- 突出了内体受体局部化在信号传导中的重要性.
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.5K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.5K
Adrenergic Receptors: β Subtype
1.9K
β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
1.9K
MAPK Signaling Cascades
5.9K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.9K
GPCRs Regulate Adenylyl Cylase Activity
5.8K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.8K
Adrenergic Receptors (Adrenoceptors): Classification
2.9K
Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors,...
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors,...
2.9K
Amplifying Signals via Enzymatic Cascade
8.7K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.7K

