Journal Hosting Service | The University of Edinburgh
Not a member yet
5244 research outputs found
Sort by
Relaxin family peptide receptors in GtoPdb v.2025.3
Get PDFRelaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [23, 125]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1, relaxin, relaxin-3 (also known as INSL7), insulin-like peptide 3 (INSL3) and INSL5. Species homologues of relaxin have distinct pharmacology and relaxin interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [268]. relaxin-3 is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [267]. INSL5 is the ligand for RXFP4 but is a weak antagonist of RXFP3. relaxin and INSL3 have multiple complex binding interactions with RXFP1 [275] and RXFP2 [138], which together with the N-terminal linker and LDLa module drive receptor activation by an unknown mechanism [270, 89]. INSL5 and relaxin-3 interact with their receptors using distinct residues in their B-chains for binding, and activation, respectively [55, 329, 158, 56]
ABCC subfamily in GtoPdb v.2025.3
No full textSubfamily ABCC contains thirteen members and nine of these transporters are referred to as the Multidrug Resistance Proteins (MRPs). The MRP proteins are found throughout nature and they mediate many important functions. They are known to be involved in ion transport, toxin secretion, and signal transduction [7, 2]
GDNF Family Receptor (GFR) in GtoPdb v.2025.3
Get PDFGDNF family receptors (GFR) are extrinsic co-receptors, where ligand binding to the extracellular domain of the glycosylphosphatidylinositol-linked cell-surface GFRs activates a transmembrane tyrosine kinase enzyme, RET. The endogenous ligands are typically dimeric, linked through disulphide bridges: glial cell-derived neurotrophic factor GDNF (211 aa); neurturin (197 aa); artemin (237 aa) and persephin (156 aa), referred to as GDNF family ligands (GFLs). There is evidence for RET-dependent and RET-independent signalling [5]. Growth/Differentiation Factor 15 (GDF15) has been shown to activate GFRAL, a transmembrane protein that similarly forms a complex with RET [8, 10]
Integrins in GtoPdb v.2025.3
Get PDFIntegrins are unusual signalling proteins that function to signal both from the extracellular environment into the cell, but also from the cytoplasm to the external of the cell. The intracellular signalling cascades associated with integrin activation focus on protein kinase activities, such as focal adhesion kinase and Src. Based on this association between extracellular signals and intracellular protein kinase activity, we have chosen to include integrins in the \u27Catalytic receptors\u27 section of the database until more stringent criteria from NC-IUPHAR allows precise definition of their classification.Integrins are heterodimeric entities, composed of α and β subunits, each 1TM proteins, which bind components of the extracellular matrix or counter-receptors expressed on other cells. One class of integrin contains an inserted domain (I) in its α subunit, and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), this I domain contains the ligand binding site. All β subunits possess a similar I-like domain, which has the capacity to bind ligand, often recognising the RGD motif. The presence of an α subunit I domain precludes ligand binding through the β subunit. Integrins provide a link between ligand and the actin cytoskeleton (through typically short intracellular domains). Integrins bind several divalent cations, including a Mg2+ ion in the I or I-like domain that is essential for ligand binding. Other cation binding sites may regulate integrin activity or stabilise the 3D structure. Integrins regulate the activity of particular protein kinases, including focal adhesion kinase and integrin-linked kinase. Cellular activation regulates integrin ligand affinity via inside-out signalling and ligand binding to integrins can regulate cellular activity via outside-in signalling.Several drugs that target integrins are in clinical use including: (1) tirofiban (αIIbβ3) for short term prevention of coronary thrombosis (abciximab, the first clinically approved (1994) chimeric monoclonal antibody, is no longer available for clinical use), (2) vedolizumab (α4β7) to reduce gastrointestinal inflammation, and (3) natalizumab (α4β1) in some cases of severe multiple sclerosis. Drugs targeting multiple integrins are under investigation for the treatment of dry eye disease, e.g., risuteganib, an anti-integrin peptide [44]
Type XV RTKs: RYK in GtoPdb v.2025.3
Get PDFThe \u27related to tyrosine kinase receptor\u27 (Ryk) is structurally atypical of the family of RTKs, particularly in the activation and ATP-binding domains, lacking kinase activity akin to ROR1/2. Similarly, however, there is evidence that RTK is involved in Wnt signalling [2]
Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2025.3
Get PDFRegulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [226, 530, 579, 584, 585, 744, 755, 445, 11]
Class A Orphans in GtoPdb v.2025.4
Get PDFThe class A orphan GPCRs have been organised into the subfamilies listed below, to better segregate them based on evidence (or lack of evidence) for endogenous ligand or surrogate ligand interactions, and potential for deorphanization
Orai channels in GtoPdb v.2025.4
Get PDFOrai channels are pore forming proteins which underlie calcium release-activated calcium (CRAC) channels. In numerous cell types, calcium influx is predominantly governed by store-operated calcium channels (SOCs). The process of store-operated calcium entry (SOCE) is orchestrated through the concerted interaction of two essential molecular components: the pore-forming Orai proteins (Orai1-3) and the endoplasmic reticulum calcium-sensing stromal interaction molecules (STIM1 and STIM2) [25]
Defending Women’s Rights: The Inter-American Court’s Role in Ensuring Justice for Gender-Based Violence Victims by Niesje Vanduffel
No full textThis paper argues that the Inter-American Court of Human Rights (IACtHR) has significantly enhanced the justiciability and remedies dimensions of women’s right to access justice in cases of gender-based violence. Through a holistic approach, the Court has demonstrated a commitment to addressing not only individual acts of violence but also the structural and systemic factors that perpetuate such violations. By analysing key jurisprudence, the paper illustrates how the IACtHR has expanded the legal standards for state accountability, strengthened due diligence obligations, and advanced reparative frameworks that go beyond individual redress to include transformative measures. Furthermore, the paper examines how national jurisdictions and international legal bodies have engaged with and integrated the Court’s jurisprudence, reinforcing its broader impact on the protection of women\u27s rights. The findings suggest that the IACtHR has played a crucial role in shaping a more robust and enforceable legal framework for gender justice in the Inter-American system and beyond
How Terrorism Ends - Accounting for Contemporary Realities 15 Years after Cronin by Pierre Musa Halime Wessel
No full textThis comment revisits Audrey Cronin\u27s How Terrorism Ends, first published in 2009, with the aim of assessing its continued relevance in light of contemporary developments. While Cronin’s framework remains a cornerstone in the study of terrorist decline, new research by scholars such as Jenna Jordan has demonstrated that Cronin’s typology can be enriched by recognizing new developments in global terrorism over time. Throughout, it addresses the new availability of terrorism data and research and developments such as the sharp increase and decrease in terrorist attacks, the rise and fall of active terrorist groups, and the emergence of new threats like cyberterrorism as reasons to revisit Cronin’s model. Her typology proves to still be relevant as a lens to assess contemporary terrorism but may also be limited in its ability to provide full explanation, suggesting the need to reassess her framework