ERBB4, Active
- Known as:
- ERBB4, Active
- Catalog number:
- Z02561
- Product Quantity:
- 10ug
- Category:
- -
- Supplier:
- Genscript
- Gene target:
- ERBB4 Active
Related genes to: ERBB4, Active
- Gene:
- ERBB4 NIH gene
- Name:
- erb-b2 receptor tyrosine kinase 4
- Previous symbol:
- -
- Synonyms:
- ALS19, HER4
- Chromosome:
- 2q34
- Locus Type:
- gene with protein product
- Date approved:
- 1995-09-07
- Date modifiied:
- 2016-10-05
Related products to: ERBB4, Active
Related articles to: ERBB4, Active
- ErbB receptor tyrosine kinases orchestrate phosphorylation-based signaling in response to extracellular ligands and are key drivers in cancer biology. Although ErbB-targeted therapies have transformed cancer care, some agents cause cardiac adverse events. Yet, the acute phosphorylation programs engaged by ErbB ligands in the adult heart remain incompletely defined. Here, we applied in vivo quantitative phosphoproteomics with dual enrichment using TiO₂ and anti-phosphotyrosine antibodies to map acute cardiac phosphorylation responses to epidermal growth factor (EGF; EGFR/ErbB1) and neuregulin-1β (NRG1β; ErbB3/ErbB4) in adult mouse hearts. EGF triggered robust receptor tyrosine kinase signaling, convergence with insulin-associated nodes independent of insulin receptor activation, and phosphorylation of calcium-handling proteins including phospholamban, SERCA, NCX1, and CaV1.2, implicating CaMK2δ. NRG1β elicited a coordinated ErbB-dependent response featuring activation of Akt, MAPK, and stress kinases, with engagement of sarcomere and metabolic modules. Comparative analysis identified shared core signaling alongside ligand-specific differences in kinase and transcription factor phosphorylation, with EGF displaying broader network breadth. These data provide a phosphorylation-centric framework for ligand-resolved ErbB signaling in the heart and offer mechanistic insight into how ErbB-targeted therapies may influence cardiac function. - Source: PubMed
Publication date: 2026/07/09
Vega Estefania TorresGalsgaard Katrine DouglasSvenningsen Mikkel SkjoldanHolst Jens JuulLundby Alicia - Hyperlipidemia is a major contributor to atherosclerotic cardiovascular disease, yet effective therapeutic strategies targeting lipid metabolism remain limited. Recent evidence has established brown adipose tissue (BAT) as an endocrine organ that specifically expresses and secretes neuregulin 4 (Nrg4), a key factor in metabolic regulation. However, the mechanism by which Nrg4 controls hepatic lipid metabolism remains unclear. Here, we investigated whether Nrg4 modulates lipid homeostasis via a hepatic Human Epidermal Growth Factor Receptor 4 (ErbB4)-dependent pathway. In hyperlipidemic apolipoprotein E-deficient mice, BAT depletion reduced circulating Nrg4 and worsened dyslipidemia, whereas recombinant Nrg4 reactivated hepatic ErbB4 signaling, alleviated steatosis, improved serum lipid profiles, and reduced atherosclerotic plaques. In AML12 hepatocytes, Nrg4 suppressed palmitate-induced lipid accumulation in an ErbB4-dependent manner. Co-culture experiments further confirmed that activated brown adipocytes protect hepatocytes through secreted Nrg4. Transcriptomic profiling identified cytochrome P450 1A1 (CYP1A1) as one of the most markedly upregulated genes following Nrg4 treatment. Since CYP1A1 is a canonical target of the aryl hydrocarbon receptor (AHR), mechanistic experiments demonstrated that Nrg4 restored the protein expression of ErbB4, AHR, and CYP1A1 that was suppressed by palmitate, and these restorative effects were abolished by ErbB4 knockdown, confirming a novel ErbB4/AHR/CYP1A1 signaling pathway. Collectively, our findings elucidate a novel BAT-liver endocrine pathway through which BAT-derived Nrg4 ameliorates hyperlipidemia and atherosclerosis, identifying a promising therapeutic target for dyslipidemia and its cardiovascular complications. - Source: PubMed
Publication date: 2026/07/08
Yang YulongHu YueWu XiqiuXu ZhianZhao XuanDai MinShi Xiaoyan - This study aims to investigate the effect of modified Xiangsha Liujunzi Decoction on adipose tissue browning-neuregulin 4(Nrg4)-liver fatty acid synthesis pathway in the rat model of both spleen deficiency and hyperlipidemia. Seventy SPF-grade male SD rats were randomly assigned into blank control(CON), high-fat diet(HFD), spleen deficiency and high-fat diet(SD-HFD), rosuvastatin(RSF), low-, medium-, and high-dose modified Xiangsha Liujunzi Decoction(XS-L, XS-M, and XS-H, respectively) groups, with 10 rats in each group. The rats in the SD-HFD, RSF, XS-L, XS-M, and XS-H groups were modeled for spleen deficiency by an improper diet combined with swimming exhaustion for a total of 15 days. The CON group was fed with a normal diet while the other groups with a high-fat diet for 10 weeks after successful modeling of spleen deficiency. The RSF, XS-L, XS-M, and XS-H groups were administrated with corresponding drugs by gavage for 8 weeks and the other groups were administrated with an equal volume of distilled water. The feeding method of each group was kept unchanged during the period of gavage. Four items of serum lipids were measured by an automatic biochemical analyzer. The pathological changes in the interscapular brown adipose tissue(BAT), abdominal white adipose tissue(WAT), and liver were observed by hematoxylin-eosin(HE) staining. The liver lipid deposition was observed by oil red O staining and the serum Nrg4 level was measured by enzyme-linked immunosorbent assay(ELISA). RT-qPCR was employed to determine the mRNA levels of peroxisome proliferator-activated receptor gamma(PPARγ), peroxisome proliferator-activated receptor gamma cofactor 1α(PGC1α), uncoupling protein 1(UCP1), and Nrg4 in the adipose tissue and liver X receptor alpha(LXRα), sterol regulatory element-binding protein-1c(SREBP-1c), acetyl-CoA carboxylase(ACC), and stearoyl-CoA desaturase 1(SCD1) in the liver tissue of rats in each group. Western blot was employed to quantify the protein levels of PPARγ, PGC1α, UCP1, and Nrg4 in the adipose tissue and Erb-B2 receptor tyrosine kinase 3(ErbB3), phosphorylated ErbB3(p-ErbB3), Erb-B2 receptor tyrosine kinase 4(ErbB4), phosphorylated ErbB4(p-ErbB4), signal transducer and activator of transcription 5(STAT5), phosphorylated STAT5(p-STAT5), LXRα, SREBP-1c, ACC, and SCD1 in the liver tissue. Compared with the CON group, the HFD and SD-HFD groups showed significantly elevated serum levels of triglycerides(TG), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), and low-density lipoprotein-cholesterol(LDL-C) and a significantly declined level of Nrg4. HE staining revealed enlarged BAT and WAT cells and increased lipid vacuoles in hepatocytes in the HFD and SD-HFD groups. The oil red O staining showed that the HFD and SD-HFD groups had more orange lipid droplets in hepatocytes than the CON group. Compared with the CON group, the SD-HFD group showed significantly down-regulated mRNA and protein levels of PPARγ, PGC1α, and Nrg4, significantly down-regulated protein levels of UCP1 in both BAT and WAT cells, and a significantly down-regulated mRNA level of UCP1 in BAT cells. In addition, the SD-HFD group showed significantly decreased p-ErbB3/ErbB3, p-ErbB4/ErbB4, and p-STAT5/STAT5 ratios and significantly up-regulated mRNA and protein levels of LXRα, SREBP-1c, ACC, and SCD1 in the liver tissue. Compared with the SD-HFD group, the RSF, XS-M, and XS-H groups showed significantly declined serum TG, TC, and LDL-C levels, and the XS-M and XS-H groups presented significantly elevated serum Nrg4 levels. In addition, these groups showed reductions in volumes of BAT and WAT cells, alleviated hepatocyte swelling, and decreased lipid droplets in hepatocytes. The mRNA and protein levels of related factors were improved in XS-M and XS-H groups compared with those in the SD-HFD group. This study indicates that modified Xiangsha Liujunzi Decoction could promote the browning of adipose tissue, increase the expression of Nrg4 in the adipose tissue, raise the level of circulating Nrg4, and reduce liver fatty acid synthesis in the rat model of both spleen deficiency and hyperlipidemia. - Source: PubMed
Qiao AiZhao NaZhang QiChe Meng-ZhuSui Guo-YuanJia Lian-Qun - Basal cell carcinoma (BCC) is the most common skin malignancy and is strongly associated with ultraviolet (UV) radiation. However, BCC arising in sun-protected areas such as the anogenital region remains poorly characterized. To compare the molecular profiles of anogenital BCC with those of BCC arising in sun-exposed skin, a retrospective analysis was performed on BCC cases identified between 2017 and 2025. Formalin-fixed, paraffin-embedded tissue samples were analyzed using a targeted next-generation sequencing panel (Oncomine Precision Assay GX). Clinicopathologic features and mutational profiles were compared. Nine anogenital BCC cases and 23 sun-exposed BCC cases were included. Mutations were identified in 14 of 23 (60.8%) sun-exposed cases, most commonly involving TP53, with additional alterations in SMO, FGFR3, ERBB2, RET, ERBB4, and PDGFRA. In contrast, no mutations were detected in the anogenital BCC group. Despite histologic similarity, anogenital BCC demonstrates a distinct molecular profile, suggesting an alternative pathogenesis. Further genomic studies are warranted. - Source: PubMed
Publication date: 2026/07/01
Ali AhlamOnur PelinMohamed AnasBello ShamsuAzad Abul KalamGoldstein DoctorHebert Tiffany - This study aims to screen pain-related genes through bioinformatics analysis and to explore their potential molecular regulatory mechanisms in pulpitis. - Source: PubMed
Publication date: 2026/06/29
He YingZhu YingYao MianfengQiu XilinJiang YeWu LihongChen XinYang Xuechao