Parathyroid hormone receptors in GtoPdb v.2021.3

The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [49]) are class B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors. The structure of a long-active PTH analogue (LA-PTH, an hybrid of PTH-(1-13) and PTHrP-(14-36)) bound to the PTH1 receptor-Gs complex has been resolved by cryo-electron microscopy [147]. Another structure of a PTH-(1-34) analog bound to a thermostabilized inactive PTH1 receptor has been obtained with X-ray crytallography [34]

Parathyroid hormone receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [47]) are family B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors

Parathyroid hormone receptors in GtoPdb v.2023.1

The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [50]) are class B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors. The structure of a long-active PTH analogue (LA-PTH, an hybrid of PTH-(1-13) and PTHrP-(14-36)) bound to the PTH1 receptor-Gs complex has been resolved by cryo-electron microscopy [148]. Another structure of a PTH-(1-34) analog bound to a thermostabilized inactive PTH1 receptor has been obtained with X-ray crytallography [35]

Earliest archaeological evidence of persistent hominin carnivory

The emergence of lithic technology by ~2.6 million years ago (Ma) is often interpreted as a correlate of increasingly recurrent hominin acquisition and consumption of animal remains. Associated faunal evidence, however, is poorly preserved prior to ~1.8 Ma, limiting our understanding of early archaeological (Oldowan) hominin carnivory. Here, we detail three large well-preserved zooarchaeological assemblages from Kanjera South, Kenya. The assemblages date to ~2.0 Ma, pre-dating all previously published archaeofaunas of appreciable size. At Kanjera, there is clear evidence that Oldowan hominins acquired and processed numerous, relatively complete, small ungulate carcasses. Moreover, they had at least occasional access to the fleshed remains of larger, wildebeest-sized animals. The overall record of hominin activities is consistent through the stratified sequence ??? spanning hundreds to thousands of years ??? and provides the earliest archaeological evidence of sustained hominin involvement with fleshed animal remains (i.e., persistent carnivory), a foraging adaptation central to many models of hominin evolution.This research was supported by funding from the National Science Foundation, Leakey Foundation, Wenner-Gren Foundation, National Geographic Society, The Leverhulme Trust, University of California, Baylor University, and the City University of New York. Additional logistical support was provided by the Smithsonian Institution???s Human Origins Program and the Peter Buck Fund for Human Origins Research, the British Institute in Eastern Africa, and the National Museums of Kenya. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Altered Selectivity of Parathyroid Hormone (PTH) and PTH-Related Protein (PTHrP) for Distinct Conformations of the PTH/PTHrP Receptor

PTH and PTHrP use the same G protein-coupled receptor, the PTH/PTHrP receptor (PTHR), to mediate their distinct biological actions. The extent to which the mechanisms by which the two ligands bind to the PTHR differ is unclear. We examined this question using several pharmacological and biophysical approaches. Kinetic dissociation and equilibrium binding assays revealed that the binding of [125I]PTHrP(1–36) to the PTHR was more sensitive to GTPγS (added to functionally uncouple PTHR-G protein complexes) than was the binding of [125I]PTH(1–34) (∼75% maximal inhibition vs. ∼20%). Fluorescence resonance energy transfer-based kinetic analyses revealed that PTHrP(1–36) bound to the PTHR more slowly and dissociated from it more rapidly than did PTH(1–34). The cAMP signaling response capacity of PTHrP(1–36) in cells decayed more rapidly than did that of PTH(1–34) (t1/2 = ∼1 vs. ∼2 h). Divergent residue 5 in the ligand, Ile in PTH and His in PTHrP, was identified as a key determinant of the altered receptor-interaction responses exhibited by the two peptides. We conclude that whereas PTH and PTHrP bind similarly to the G protein-coupled PTHR conformation (RG), PTH has a greater capacity to bind to the G protein-uncoupled conformation (R0) and, hence, can produce cumulatively greater signaling responses (via R0→RG isomerization) than can PTHrP. Such conformational selectivity may relate to the distinct modes by which PTH and PTHrP act biologically, endocrine vs. paracrine, and may help explain reported differences in the effects that the ligands have on calcium and bone metabolism when administered to humans

Tooth-mark frequencies and long bone portion representation: results from modern experiments and excavations at KJS.

<p>Portions defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone-0062174-t002" target="_blank">Table 2</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174.s001" target="_blank">Table S1</a>. ‘Shafts’ include both near-epiphyseal and mid-shaft specimens. Complete bones are not included in epiphysis-to-shaft calculations (number of complete bones = 2, 7, and 1; beds KS-1 through KS-3, respectively). Ellipses outline the range of results in experimental feeding scenarios involving: carnivores-only, hominins-only, or a sequence of hominins-then-carnivores (i.e., ‘hominin-first’). The dashed line is a published least-squares regression for hominin-first scenarios <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Blumenschine1" target="_blank">[22]</a>. Hominin-only scenarios have no tooth marks, hence the placement of the ellipse beneath the x-axis. KJS data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone-0062174-t002" target="_blank">Table 2</a> are for summed body sizes. KJS epiphysis-to-shaft ratios: 0.26, 0.22, and 0.19 for beds KS-1 though KS-3 respectively. KJS tooth-mark data displayed as solid vertical bars, with bars representing the range of analysts’ results. Results from Kanjera are consistent with hominin-first contexts.</p

Skeletal element representation for (A) small and (B) medium-sized bovids, Bed KS-1.

<p>Abundance data presented as percent minimum animal units (%MAU), calculated following the literature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Lyman1" target="_blank">[43]</a>. KJS data derived from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174.s003" target="_blank">Table S3</a>. 100% MAU = 6 for small bovids, 9 for medium-sized bovids. Similar patterns of skeletal element representation are present in Beds KS-2 and KS-3.</p

Faunal and lithic inventory.

<p>NISP (number of identified specimens) and MNI (minimum number of individuals) are defined and quantified following the literature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Lyman1" target="_blank">[43]</a>. ‘Total NISP’ reflects the sum of specimens recovered with coordinate data and included in this study. Tens of thousands of non-identifiable bone and tooth fragments <2 cm are omitted from this study. Fossils from conglomeratic facies (CP levels) are poorly preserved <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Plummer2" target="_blank">[49]</a>, and are likewise excluded from this study: KS-2CP (n = 259), KS-3CP (n = 102). Macro-mammals are defined here as weighing >5 kg. Macro-mammal NISP values are total sums and, in parentheses, the sum of specimens identified beyond Linnean class. %NISP and %MNI include macro-mammals only. Faunal and lithic counts are from the literature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Ferraro1" target="_blank">[17]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Braun4" target="_blank">[55]</a>.</p

Location of Kanjera along the modern shoreline of Lake Victoria, East Africa.

<p>(A) Kanjera lies to the immediate northeast of Homa Mountain, a volcanic complex active from the middle Miocene to the Pleistocene. The Winam Gulf fills the western end of the Nyanza Rift, an E-W graben with origins in the early Miocene. (B) Beds KS-1 through KS-3 of the Kanjera Formation (Southern Member) sample floodplain and low-aspect channel contexts originally deposited between the mountain and the nearby shores of a shallow lake <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062174#pone.0062174-Plummer2" target="_blank">[49]</a>. Satellite imagery from USGS and NASA.</p