在GH-PitNET中的GIPR:分子和功能洞察力
Mattia Dalle Nogare1, Serena Avallone1,2, Eva Galletta1
1Department of Biology, University of Padova, Padova, Italy.
Endocrine-related cancer
|October 9, 2025
概括
在垂体瘤中依赖葡萄糖的胰岛素型多受体 (GIPR) 激活增强激素分泌并改变细胞信号通路. GIPR可能会影响壮症的治疗反应,但不会影响瘤的生长.
科学领域:
- 内分泌学和分子生物学
- 下垂体神经内分泌瘤 (PitNETs) 是一种
背景情况:
- 由GH分泌PitNETs引起的巨,通常表现为对体静止素受体连接体 (SRLs) 的抗性.
- 葡萄糖依赖型胰岛素型多受体 (GIPR) 的过度表达与GH-PitNETs中的瘤异质性和特定的临床特征有关.
研究的目的:
- 为了研究GIPR在体细胞中的功能作用.
- 在GH-PitNET模型中探索GIPR激活对信号通路,激素分泌和细胞行为的影响.
主要方法:
- 产生稳定的人类GIPR表达GH3细胞 (GH3hGIPR) 并与对照细胞进行比较.
- 测量cAMP/PKA,MAPK/ERK信号传递,激素分泌 (GH,益生菌素) 和细胞内的功能测定.
- 转录组分析以确定差异性的基因表达模式.
主要成果:
- GIPR激活诱导了cAMP/PKA和MAPK/ERK信号,增强了GH和益生菌分泌,增加了振荡.
- 转录组分析揭示了与细胞运动,神经元发育和细胞外矩阵重塑相关的改变基因表达.
- 过度表达GIPR并没有影响细胞增殖或活力.
结论:
- GIPR信号传递在体细胞功能中起着重要作用,影响激素分泌和细胞通路.
- GIPR可能会影响壮症的治疗反应,但其在瘤发生中的直接作用需要进一步调查.
- 结果强调GIPR是GH-PitNET异质性和SRL敏感性的潜在因素.
相关概念视频
GPCRs Regulate Adenylyl Cylase Activity
7.3K
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...
7.3K
GPI Anchoring of Proteins in the ER Membrane
5.3K
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
5.3K
Activation and Inactivation of G Proteins
10.9K
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...
10.9K
G Protein-coupled Receptors
16.5K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
16.5K
IP3/DAG Signaling Pathway
14.3K
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...
14.3K
Phosphoinositides and PIPs
10.1K
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...
10.1K


