FLJ20433 Blocking Peptide
- Known as:
- FLJ20433 Blocking Peptide
- Catalog number:
- 33r-6053
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- FLJ20433 Blocking Peptide
Related genes to: FLJ20433 Blocking Peptide
- Gene:
- EXD3 NIH gene
- Name:
- exonuclease 3'-5' domain containing 3
- Previous symbol:
- -
- Synonyms:
- LOC54932, FLJ20433, mut-7
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2009-03-04
- Date modifiied:
- 2014-11-19
Related products to: FLJ20433 Blocking Peptide
Related articles to: FLJ20433 Blocking Peptide
- The glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target for type 2 diabetes and obesity. Agonists showing bias in favour of G protein signalling over β-arrestin recruitment and GLP-1R internalisation, e.g. tirzepatide and orforglipron, have favourable clinical efficacy profiles. However, understanding of the effects of biased agonism has been hampered by differences in ligand properties such as affinity, efficacy, stability and pharmacokinetics. Here we used GLP-1R C-tail mutations that inhibit phosphorylation to mimic G protein-biased GLP-1R agonism without the need for ligand modifications. - Source: PubMed
Publication date: 2026/01/20
Tran Hanh DuyenZuo YimingWong CarissaPollard AliceBloom SteveJones Ben - Diabetic kidney disease (DKD) is a major complication of diabetes, with genetic factors contributing to its progression. Although genome-wide association studies (GWAS) have identified common variants, the role of low-frequency and rare coding variants remains underexplored. - Source: PubMed
Publication date: 2025/10/22
Sandholm NiinaCole Joanne BNair VijiBrennan EoinGiardini ElenaHaukka Jani KHa EunjiSyreeni AnnaDahlström Emma HSalem Rany MFermin DamianMercader JosepSmyth LauraHill ClaireMychaleckyj JosyfMcGurnaghan StuartMiller Rachel GCostacou TinaKlein Barbara E KSnell-Bergeon JanetPaterson Andrew DVerkauskiene RasaSokolovska JelizavetaPanduru Nicolae MirceaZerbini GianpaoloBrismar KerstinKrolewski Andrzej SHarjutsalo ValmaRossing PeterHadjadj SamyMcKay GarethMcKnight Amy JayneMaxwell Alexander PSusztak KatalinGodson CatherineKretzler MatthiasHirschhorn Joel NFlorez Jose CGroop Per-Henrik - Internalisation of G protein-coupled receptors (GPCRs) can contribute to altered cellular responses by directing signalling from non-canonical locations, such as endosomes. If signalling processes are locally constrained, active receptors in different subcellular locations could produce different downstream effects. This phenomenon may be relevant to the optimal targeting of the glucagon-like peptide-1 receptor (GLP-1R), a type 2 diabetes and obesity target GPCR for which several ligands with varying internalisation tendency have been discovered. To investigate, we compared the signalling localisation effects of two prototypical GLP-1RAs with opposite signal bias and effects on GLP-1R trafficking: exendin-asp3 (ExD3), a full agonist that drives rapid internalisation, and exendin-phe1 (ExF1), which shows much slower internalisation. After using bioorthogonal labelling and fluorescent agonist conjugates to verify the divergent trafficking patterns of ExF1 and ExD3 in β-cell lines and primary pancreatic islets, we used live cell biosensors to monitor signalling at different subcellular locations. This revealed that cAMP/PKA/ERK signalling in β-cells is in fact distributed widely across the cell over short- (<5 min) and medium-term (up to 60 min) stimulation at pharmacological (>10 pM) concentrations, with no major differences in signal localisation that could be linked to internalised versus cell surface-bound GLP-1R. Moreover, washout experiments highlighted that, whilst fast-internalising ExD3 shows much greater accumulation and binding to GLP-1R in endosomes than slow-internalising ExF1, it is a rather inefficient driver of both cAMP production in β-cells and insulin secretion from perfused rat pancreata. These data provide a greater understanding of the cellular effects of biased GLP-1R agonism. - Source: PubMed
Publication date: 2025/12/12
Chen ShiqianLobato Carolina BWong CarissaManchanda YusmanViloria KatrinaDavies IonaAndersen Daniel BAst JuliaSloop Kyle WHodson David JBroichhagen JohannesBloom SteveHolst Jens JTan TriciaTomas AlejandraJones Ben - Apurinic/apyrimidinic sites are one of the most frequent spontaneous lesions in DNA. Evolutionarily conserved AP endonucleases (ExoIII and EndoIV families) incise the DNA backbone 5' to the AP site and the cleaved AP sites are subsequently repaired by the base excision repair machinery. AP endonucleases additionally exhibit 3'-5' exonuclease activity. Novel AP endonucleases that are not member of AP endonuclease families keep being reported and exhibit 3'-5' exonuclease activity and other important DNA processing. Interestingly, human and mouse WRN helicases contain a 3'-5' exonuclease domain, but the precise functional roles of the exonuclease activity in vivo remain unclear. We searched for WRN-like exonuclease proteins in the Caenorhabditis elegans database and found a new gene, zk1098.3, which shows a high similarity to human EXD3. Here, we assigned zk1098.3 to exd3-1. We cloned exd3-1 from an ORF clone and purified the recombinant EXD3-1 protein. We found that EXD3-1 displays incision at AP sites and exonucleolytic digestion on the nicked AP site and that EXD3-1 is involved in recovery from replication stress-induced cell cycle arrest. This work suggests that EXD3-1 either plays a role in base excision repair, although the extent of this repair remains to be determined, or has a specialized DNA damage response function. - Source: PubMed
Publication date: 2025/10/31
Choi SeoyunPham Hoa ThiAhn Byungchan - [D,G,K.C16 diacid]exendin-4 (acyl-ExD3) and [F,G,K.C16 diacid]exendin-4 (acyl-ExF1) are oppositely biased glucagon-like peptide-1 (GLP-1) receptor agonists that preferentially promote β-arrestin recruitment or G protein-induced signalling, respectively. The latter is more favourable in glycaemic control and induces a steeper reduction in body weight in diet-induced obese mice. Here, we compared the effects of G protein-biased agonist acyl-ExF1 to those of β-arrestin-biased agonist acyl-ExD3 on lipid metabolism in hyperlipidaemic mice. - Source: PubMed
Publication date: 2025/04/02
Modder MelanieTomas AlejandraAfkir SalwaPronk Amanda C MStreefland Trea C MLalai Reshma Avan Eenige RobinRensen Patrick C NJones BenKooijman Sander